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1. Examining temporal trends in psychological distress and the co-occurrence of common substance use in a population-based sample of grade 7–12 students from 2013 to 2019

Author: Halladay, J., Sunderland, M., Chapman, C., Repchuck, R., Georgiades, K., Boak, A., Hamilton, H. A., and Slade, T.
Published: 2024
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2. Playing for more than winning: Exploring sports participation, physical activity, and belongingness and their relationship with patterns of adolescent substance use and mental health

Author: Halladay, J., Ogrodnik, M., Farag Alla, J., Sunderland, M., Gardner, L.A., and Georgiades, K.
Published: 2024
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3. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Author: Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., Swanton C., Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., and Swanton C.
Abstract: The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.
Published: 2024

4. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

Author: Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., Moore D. A., Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., and Moore D. A.
Abstract: The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma.
Published: 2024

5. Body composition and lung cancer-associated cachexia in TRACERx

Author: Al-Sawaf, O, Weiss, J, Skrzypski, M, Lam, J, Karasaki, T, Zambrana, F, Kidd, A, Frankell, A, Watkins, T, Martinez-Ruiz, C, Puttick, C, Black, J, Huebner, A, Bakir, M, Sokac, M, Collins, S, Veeriah, S, Magno, N, Naceur-Lombardelli, C, Prymas, P, Toncheva, A, Ward, S, Jayanth, N, Salgado, R, Bridge, C, Christiani, D, Mak, R, Bay, C, Rosenthal, M, Sattar, N, Welsh, P, Liu, Y, Perrimon, N, Popuri, K, Beg, M, Mcgranahan, N, Hackshaw, A, Breen, D, O'Rahilly, S, Birkbak, N, Aerts, H, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Kisistok, J, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Moore, D, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Cadieux, E, Lim, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Pich, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Swanton, C, Al-Sawaf O., Weiss J., Skrzypski M., Lam J. M., Karasaki T., Zambrana F., Kidd A. C., Frankell A. M., Watkins T. B. K., Martinez-Ruiz C., Puttick C., Black J. R. M., Huebner A., Bakir M. A., Sokac M., Collins S., Veeriah S., Magno N., Naceur-Lombardelli C., Prymas P., Toncheva A., Ward S., Jayanth N., Salgado R., Bridge C. P., Christiani D. C., Mak R. H., Bay C., Rosenthal M., Sattar N., Welsh P., Liu Y., Perrimon N., Popuri K., Beg M. F., McGranahan N., Hackshaw A., Breen D. M., O'Rahilly S., Birkbak N. J., Aerts H. J. W. L., Aerts H. J., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Kisistok J., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Moore D. A., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Cadieux E. L., Lim E. L., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Pich O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., Swanton C., Al-Sawaf, O, Weiss, J, Skrzypski, M, Lam, J, Karasaki, T, Zambrana, F, Kidd, A, Frankell, A, Watkins, T, Martinez-Ruiz, C, Puttick, C, Black, J, Huebner, A, Bakir, M, Sokac, M, Collins, S, Veeriah, S, Magno, N, Naceur-Lombardelli, C, Prymas, P, Toncheva, A, Ward, S, Jayanth, N, Salgado, R, Bridge, C, Christiani, D, Mak, R, Bay, C, Rosenthal, M, Sattar, N, Welsh, P, Liu, Y, Perrimon, N, Popuri, K, Beg, M, Mcgranahan, N, Hackshaw, A, Breen, D, O'Rahilly, S, Birkbak, N, Aerts, H, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Kisistok, J, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Moore, D, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Cadieux, E, Lim, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Pich, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Swanton, C, Al-Sawaf O., Weiss J., Skrzypski M., Lam J. M., Karasaki T., Zambrana F., Kidd A. C., Frankell A. M., Watkins T. B. K., Martinez-Ruiz C., Puttick C., Black J. R. M., Huebner A., Bakir M. A., Sokac M., Collins S., Veeriah S., Magno N., Naceur-Lombardelli C., Prymas P., Toncheva A., Ward S., Jayanth N., Salgado R., Bridge C. P., Christiani D. C., Mak R. H., Bay C., Rosenthal M., Sattar N., Welsh P., Liu Y., Perrimon N., Popuri K., Beg M. F., McGranahan N., Hackshaw A., Breen D. M., O'Rahilly S., Birkbak N. J., Aerts H. J. W. L., Aerts H. J., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Kisistok J., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Moore D. A., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Cadieux E. L., Lim E. L., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Pich O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., and Swanton C.
Abstract: Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial–mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC.
Published: 2023

6. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author: Karasaki, T, Moore, D, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Magno, N, Ward, S, Bakir, M, Watkins, T, Grigoriadis, K, Huebner, A, Hill, M, Frankell, A, Abbosh, C, Puttick, C, Zhai, H, Gimeno-Valiente, F, Saghafinia, S, Kanu, N, Dietzen, M, Pich, O, Lim, E, Martinez-Ruiz, C, Black, J, Biswas, D, Campbell, B, Lee, C, Colliver, E, Enfield, K, Hessey, S, Hiley, C, Zaccaria, S, Litchfield, K, Birkbak, N, Cadieux, E, Demeulemeester, J, Van Loo, P, Adusumilli, P, Tan, K, Cheema, W, Sanchez-Vega, F, Jones, D, Rekhtman, N, Travis, W, Hackshaw, A, Marafioti, T, Salgado, R, Le Quesne, J, Nicholson, A, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Castignani, C, Bailey, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Mcgranahan, N, Swanton, C, Jamal-Hanjani, M, Karasaki T., Moore D. A., Veeriah S., Naceur-Lombardelli C., Toncheva A., Magno N., Ward S., Bakir M. A., Watkins T. B. K., Grigoriadis K., Huebner A., Hill M. S., Frankell A. M., Abbosh C., Puttick C., Zhai H., Gimeno-Valiente F., Saghafinia S., Kanu N., Dietzen M., Pich O., Lim E. L., Martinez-Ruiz C., Black J. R. M., Biswas D., Campbell B. B., Lee C., Colliver E., Enfield K. S. S., Hessey S., Hiley C. T., Zaccaria S., Litchfield K., Birkbak N. J., Cadieux E. L., Demeulemeester J., Van Loo P., Adusumilli P. S., Tan K. S., Cheema W., Sanchez-Vega F., Jones D. R., Rekhtman N., Travis W. D., Hackshaw A., Marafioti T., Salgado R., Le Quesne J., Nicholson A. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Castignani C., Bailey C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Kassiotis G., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., McGranahan N., Swanton C., Jamal-Hanjani M., Karasaki, T, Moore, D, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Magno, N, Ward, S, Bakir, M, Watkins, T, Grigoriadis, K, Huebner, A, Hill, M, Frankell, A, Abbosh, C, Puttick, C, Zhai, H, Gimeno-Valiente, F, Saghafinia, S, Kanu, N, Dietzen, M, Pich, O, Lim, E, Martinez-Ruiz, C, Black, J, Biswas, D, Campbell, B, Lee, C, Colliver, E, Enfield, K, Hessey, S, Hiley, C, Zaccaria, S, Litchfield, K, Birkbak, N, Cadieux, E, Demeulemeester, J, Van Loo, P, Adusumilli, P, Tan, K, Cheema, W, Sanchez-Vega, F, Jones, D, Rekhtman, N, Travis, W, Hackshaw, A, Marafioti, T, Salgado, R, Le Quesne, J, Nicholson, A, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Castignani, C, Bailey, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Mcgranahan, N, Swanton, C, Jamal-Hanjani, M, Karasaki T., Moore D. A., Veeriah S., Naceur-Lombardelli C., Toncheva A., Magno N., Ward S., Bakir M. A., Watkins T. B. K., Grigoriadis K., Huebner A., Hill M. S., Frankell A. M., Abbosh C., Puttick C., Zhai H., Gimeno-Valiente F., Saghafinia S., Kanu N., Dietzen M., Pich O., Lim E. L., Martinez-Ruiz C., Black J. R. M., Biswas D., Campbell B. B., Lee C., Colliver E., Enfield K. S. S., Hessey S., Hiley C. T., Zaccaria S., Litchfield K., Birkbak N. J., Cadieux E. L., Demeulemeester J., Van Loo P., Adusumilli P. S., Tan K. S., Cheema W., Sanchez-Vega F., Jones D. R., Rekhtman N., Travis W. D., Hackshaw A., Marafioti T., Salgado R., Le Quesne J., Nicholson A. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Castignani C., Bailey C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Kassiotis G., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., McGranahan N., Swanton C., and Jamal-Hanjani M.
Abstract: Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and ‘tumor spread through air spaces’ were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk.
Published: 2023

7. Genomic–transcriptomic evolution in lung cancer and metastasis

Author: Martinez-Ruiz, C, Black, J, Puttick, C, Hill, M, Demeulemeester, J, Larose Cadieux, E, Thol, K, Jones, T, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Prymas, P, Rowan, A, Ward, S, Cubitt, L, Athanasopoulou, F, Pich, O, Karasaki, T, Moore, D, Salgado, R, Colliver, E, Castignani, C, Dietzen, M, Huebner, A, Al Bakir, M, Tanic, M, Watkins, T, Lim, E, Al-Rashed, A, Lang, D, Clements, J, Cook, D, Rosenthal, R, Wilson, G, Frankell, A, de Carne Trecesson, S, East, P, Kanu, N, Litchfield, K, Birkbak, N, Hackshaw, A, Beck, S, Van Loo, P, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Bakir, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Karamani, A, Chain, B, Campbell, B, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Martinez-Ruiz C., Black J. R. M., Puttick C., Hill M. S., Demeulemeester J., Larose Cadieux E., Thol K., Jones T. P., Veeriah S., Naceur-Lombardelli C., Toncheva A., Prymas P., Rowan A., Ward S., Cubitt L., Athanasopoulou F., Pich O., Karasaki T., Moore D. A., Salgado R., Colliver E., Castignani C., Dietzen M., Huebner A., Al Bakir M., Tanic M., Watkins T. B. K., Lim E. L., Al-Rashed A. M., Lang D., Clements J., Cook D. E., Rosenthal R., Wilson G. A., Frankell A. M., de Carne Trecesson S., East P., Kanu N., Litchfield K., Birkbak N. J., Hackshaw A., Beck S., Van Loo P., Jamal-Hanjani M., McGranahan N., Swanton C., Bakir M. A., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Karamani A., Chain B., Campbell B. B., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Martinez-Ruiz, C, Black, J, Puttick, C, Hill, M, Demeulemeester, J, Larose Cadieux, E, Thol, K, Jones, T, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Prymas, P, Rowan, A, Ward, S, Cubitt, L, Athanasopoulou, F, Pich, O, Karasaki, T, Moore, D, Salgado, R, Colliver, E, Castignani, C, Dietzen, M, Huebner, A, Al Bakir, M, Tanic, M, Watkins, T, Lim, E, Al-Rashed, A, Lang, D, Clements, J, Cook, D, Rosenthal, R, Wilson, G, Frankell, A, de Carne Trecesson, S, East, P, Kanu, N, Litchfield, K, Birkbak, N, Hackshaw, A, Beck, S, Van Loo, P, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Bakir, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Karamani, A, Chain, B, Campbell, B, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Martinez-Ruiz C., Black J. R. M., Puttick C., Hill M. S., Demeulemeester J., Larose Cadieux E., Thol K., Jones T. P., Veeriah S., Naceur-Lombardelli C., Toncheva A., Prymas P., Rowan A., Ward S., Cubitt L., Athanasopoulou F., Pich O., Karasaki T., Moore D. A., Salgado R., Colliver E., Castignani C., Dietzen M., Huebner A., Al Bakir M., Tanic M., Watkins T. B. K., Lim E. L., Al-Rashed A. M., Lang D., Clements J., Cook D. E., Rosenthal R., Wilson G. A., Frankell A. M., de Carne Trecesson S., East P., Kanu N., Litchfield K., Birkbak N. J., Hackshaw A., Beck S., Van Loo P., Jamal-Hanjani M., McGranahan N., Swanton C., Bakir M. A., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Karamani A., Chain B., Campbell B. B., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., and Thomas M.
Abstract: Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis.
Published: 2023

8. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Author: Abbosh, C, Frankell, A, Harrison, T, Kisistok, J, Garnett, A, Johnson, L, Veeriah, S, Moreau, M, Chesh, A, Chaunzwa, T, Weiss, J, Schroeder, M, Ward, S, Grigoriadis, K, Shahpurwalla, A, Litchfield, K, Puttick, C, Biswas, D, Karasaki, T, Black, J, Martinez-Ruiz, C, Bakir, M, Pich, O, Watkins, T, Lim, E, Huebner, A, Moore, D, Godin-Heymann, N, L'Hernault, A, Bye, H, Odell, A, Roberts, P, Gomes, F, Patel, A, Manzano, E, Hiley, C, Carey, N, Riley, J, Cook, D, Hodgson, D, Stetson, D, Barrett, J, Kortlever, R, Evan, G, Hackshaw, A, Daber, R, Shaw, J, Aerts, H, Licon, A, Stahl, J, Jamal-Hanjani, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Birkbak, N, Mcgranahan, N, Swanton, C, Abbosh C., Frankell A. M., Harrison T., Kisistok J., Garnett A., Johnson L., Veeriah S., Moreau M., Chesh A., Chaunzwa T. L., Weiss J., Schroeder M. R., Ward S., Grigoriadis K., Shahpurwalla A., Litchfield K., Puttick C., Biswas D., Karasaki T., Black J. R. M., Martinez-Ruiz C., Bakir M. A., Pich O., Watkins T. B. K., Lim E. L., Huebner A., Moore D. A., Godin-Heymann N., L'Hernault A., Bye H., Odell A., Roberts P., Gomes F., Patel A. J., Manzano E., Hiley C. T., Carey N., Riley J., Cook D. E., Hodgson D., Stetson D., Barrett J. C., Kortlever R. M., Evan G. I., Hackshaw A., Daber R. D., Shaw J. A., Aerts H. J. W. L., Licon A., Stahl J., Jamal-Hanjani M., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Toncheva A., Chain B., Campbell B. B., Castignani C., Bailey C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Birkbak N. J., McGranahan N., Swanton C., Abbosh, C, Frankell, A, Harrison, T, Kisistok, J, Garnett, A, Johnson, L, Veeriah, S, Moreau, M, Chesh, A, Chaunzwa, T, Weiss, J, Schroeder, M, Ward, S, Grigoriadis, K, Shahpurwalla, A, Litchfield, K, Puttick, C, Biswas, D, Karasaki, T, Black, J, Martinez-Ruiz, C, Bakir, M, Pich, O, Watkins, T, Lim, E, Huebner, A, Moore, D, Godin-Heymann, N, L'Hernault, A, Bye, H, Odell, A, Roberts, P, Gomes, F, Patel, A, Manzano, E, Hiley, C, Carey, N, Riley, J, Cook, D, Hodgson, D, Stetson, D, Barrett, J, Kortlever, R, Evan, G, Hackshaw, A, Daber, R, Shaw, J, Aerts, H, Licon, A, Stahl, J, Jamal-Hanjani, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Birkbak, N, Mcgranahan, N, Swanton, C, Abbosh C., Frankell A. M., Harrison T., Kisistok J., Garnett A., Johnson L., Veeriah S., Moreau M., Chesh A., Chaunzwa T. L., Weiss J., Schroeder M. R., Ward S., Grigoriadis K., Shahpurwalla A., Litchfield K., Puttick C., Biswas D., Karasaki T., Black J. R. M., Martinez-Ruiz C., Bakir M. A., Pich O., Watkins T. B. K., Lim E. L., Huebner A., Moore D. A., Godin-Heymann N., L'Hernault A., Bye H., Odell A., Roberts P., Gomes F., Patel A. J., Manzano E., Hiley C. T., Carey N., Riley J., Cook D. E., Hodgson D., Stetson D., Barrett J. C., Kortlever R. M., Evan G. I., Hackshaw A., Daber R. D., Shaw J. A., Aerts H. J. W. L., Licon A., Stahl J., Jamal-Hanjani M., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Toncheva A., Chain B., Campbell B. B., Castignani C., Bailey C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Birkbak N. J., McGranahan N., and Swanton C.
Abstract: Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.
Published: 2023

9. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Author: Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., Kassiotis G., Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., and Kassiotis G.
Abstract: B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.
Published: 2023

10. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author: Frankell, A, Dietzen, M, Al Bakir, M, Lim, E, Karasaki, T, Ward, S, Veeriah, S, Colliver, E, Huebner, A, Bunkum, A, Hill, M, Grigoriadis, K, Moore, D, Black, J, Liu, W, Thol, K, Pich, O, Watkins, T, Naceur-Lombardelli, C, Cook, D, Salgado, R, Wilson, G, Bailey, C, Angelova, M, Bentham, R, Martinez-Ruiz, C, Abbosh, C, Nicholson, A, Le Quesne, J, Biswas, D, Rosenthal, R, Puttick, C, Hessey, S, Lee, C, Prymas, P, Toncheva, A, Smith, J, Xing, W, Nicod, J, Price, G, Kerr, K, Naidu, B, Middleton, G, Blyth, K, Fennell, D, Forster, M, Lee, S, Falzon, M, Hewish, M, Shackcloth, M, Benafif, S, Russell, P, Boleti, E, Krebs, M, Lester, J, Papadatos-Pastos, D, Ahmad, T, Thakrar, R, Lawrence, D, Navani, N, Janes, S, Dive, C, Blackhall, F, Summers, Y, Cave, J, Marafioti, T, Herrero, J, Quezada, S, Peggs, K, Schwarz, R, Van Loo, P, Miedema, D, Birkbak, N, Hiley, C, Hackshaw, A, Zaccaria, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Gilbert, K, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Aerts, H, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Demeulemeester, J, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Rane, J, Lam, J, Hartley, J, Enfield, K, Selvaraju, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Borg, E, Wilson, J, Procter, A, Ahmed, A, Taylor, M, Nair, A, Patrini, D, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Danson, S, Robinson, L, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Frankell A. M., Dietzen M., Al Bakir M., Lim E. L., Karasaki T., Ward S., Veeriah S., Colliver E., Huebner A., Bunkum A., Hill M. S., Grigoriadis K., Moore D. A., Black J. R. M., Liu W. K., Thol K., Pich O., Watkins T. B. K., Naceur-Lombardelli C., Cook D. E., Salgado R., Wilson G. A., Bailey C., Angelova M., Bentham R., Martinez-Ruiz C., Abbosh C., Nicholson A. G., Le Quesne J., Biswas D., Rosenthal R., Puttick C., Hessey S., Lee C., Prymas P., Toncheva A., Smith J., Xing W., Nicod J., Price G., Kerr K. M., Naidu B., Middleton G., Blyth K. G., Fennell D. A., Forster M. D., Lee S. M., Falzon M., Hewish M., Shackcloth M. J., Lim E., Benafif S., Russell P., Boleti E., Krebs M. G., Lester J. F., Papadatos-Pastos D., Ahmad T., Thakrar R. M., Lawrence D., Navani N., Janes S. M., Dive C., Blackhall F. H., Summers Y., Cave J., Marafioti T., Herrero J., Quezada S. A., Peggs K. S., Schwarz R. F., Van Loo P., Miedema D. M., Birkbak N. J., Hiley C. T., Hackshaw A., Zaccaria S., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Cheyne H., Khalil M., Richardson S., Cruickshank T., Gilbert K., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Aerts H. J. W. L., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Demeulemeester J., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Rane J. K., Lam J. M., Hartley J. A., Enfield K. S. S., Selvaraju K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Leung M., Escudero M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Borg E., Wilson J., Procter A. J., Ahmed A., Taylor M. N., Nair A., Patrini D., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Scarlett L., Richards J., Ingram P., Austin S., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Danson S., Robinson L., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., McGranahan N., Swanton C., Frankell, A, Dietzen, M, Al Bakir, M, Lim, E, Karasaki, T, Ward, S, Veeriah, S, Colliver, E, Huebner, A, Bunkum, A, Hill, M, Grigoriadis, K, Moore, D, Black, J, Liu, W, Thol, K, Pich, O, Watkins, T, Naceur-Lombardelli, C, Cook, D, Salgado, R, Wilson, G, Bailey, C, Angelova, M, Bentham, R, Martinez-Ruiz, C, Abbosh, C, Nicholson, A, Le Quesne, J, Biswas, D, Rosenthal, R, Puttick, C, Hessey, S, Lee, C, Prymas, P, Toncheva, A, Smith, J, Xing, W, Nicod, J, Price, G, Kerr, K, Naidu, B, Middleton, G, Blyth, K, Fennell, D, Forster, M, Lee, S, Falzon, M, Hewish, M, Shackcloth, M, Benafif, S, Russell, P, Boleti, E, Krebs, M, Lester, J, Papadatos-Pastos, D, Ahmad, T, Thakrar, R, Lawrence, D, Navani, N, Janes, S, Dive, C, Blackhall, F, Summers, Y, Cave, J, Marafioti, T, Herrero, J, Quezada, S, Peggs, K, Schwarz, R, Van Loo, P, Miedema, D, Birkbak, N, Hiley, C, Hackshaw, A, Zaccaria, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Gilbert, K, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Aerts, H, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Demeulemeester, J, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Rane, J, Lam, J, Hartley, J, Enfield, K, Selvaraju, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Borg, E, Wilson, J, Procter, A, Ahmed, A, Taylor, M, Nair, A, Patrini, D, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Danson, S, Robinson, L, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Frankell A. M., Dietzen M., Al Bakir M., Lim E. L., Karasaki T., Ward S., Veeriah S., Colliver E., Huebner A., Bunkum A., Hill M. S., Grigoriadis K., Moore D. A., Black J. R. M., Liu W. K., Thol K., Pich O., Watkins T. B. K., Naceur-Lombardelli C., Cook D. E., Salgado R., Wilson G. A., Bailey C., Angelova M., Bentham R., Martinez-Ruiz C., Abbosh C., Nicholson A. G., Le Quesne J., Biswas D., Rosenthal R., Puttick C., Hessey S., Lee C., Prymas P., Toncheva A., Smith J., Xing W., Nicod J., Price G., Kerr K. M., Naidu B., Middleton G., Blyth K. G., Fennell D. A., Forster M. D., Lee S. M., Falzon M., Hewish M., Shackcloth M. J., Lim E., Benafif S., Russell P., Boleti E., Krebs M. G., Lester J. F., Papadatos-Pastos D., Ahmad T., Thakrar R. M., Lawrence D., Navani N., Janes S. M., Dive C., Blackhall F. H., Summers Y., Cave J., Marafioti T., Herrero J., Quezada S. A., Peggs K. S., Schwarz R. F., Van Loo P., Miedema D. M., Birkbak N. J., Hiley C. T., Hackshaw A., Zaccaria S., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Cheyne H., Khalil M., Richardson S., Cruickshank T., Gilbert K., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Aerts H. J. W. L., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Demeulemeester J., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Rane J. K., Lam J. M., Hartley J. A., Enfield K. S. S., Selvaraju K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Leung M., Escudero M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Borg E., Wilson J., Procter A. J., Ahmed A., Taylor M. N., Nair A., Patrini D., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Scarlett L., Richards J., Ingram P., Austin S., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Danson S., Robinson L., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., McGranahan N., and Swanton C.
Abstract: Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.
Published: 2023

11. Playing for more than winning: Exploring sports participation, physical activity, and belongingness and their relationship with patterns of adolescent substance use and mental health

Author: Halladay, J., primary, Ogrodnik, M., additional, Farag Alla, J., additional, Sunderland, M., additional, Gardner, L.A., additional, and Georgiades, K., additional
Published: 2023
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12. Validity of the PROMIS depression and anxiety common metrics in an online sample of Australian adults

Author: Sunderland, M., Batterham, P., Calear, A., and Carragher, N.
Published: 2018

13. Understanding suicidal transitions in Australian adults: protocol for the LifeTrack prospective longitudinal cohort study

Author: Batterham, PJ, Gendi, M, Christensen, H, Calear, AL, Shand, F, Sunderland, M, Borschmann, R, Banfield, M, O'Dea, B, Larsen, M, Heffernan, C, Kazan, D, Werner-Seidler, A, Mackinnon, AJ, Hielscher, E, Han, J, Boydell, KM, Leach, L, Farrer, LM, Batterham, PJ, Gendi, M, Christensen, H, Calear, AL, Shand, F, Sunderland, M, Borschmann, R, Banfield, M, O'Dea, B, Larsen, M, Heffernan, C, Kazan, D, Werner-Seidler, A, Mackinnon, AJ, Hielscher, E, Han, J, Boydell, KM, Leach, L, and Farrer, LM
Abstract: BACKGROUND: The factors that influence transition from suicidal ideation to a suicide attempt or remission of suicidal thoughts are poorly understood. Despite an abundance of research on risk factors for suicidal ideation, no large-scale longitudinal population-based studies have specifically recruited people with suicidal ideation to examine the mechanisms underlying critical transitions to either suicide attempt or recovery from suicidal ideation. Without longitudinal data on the psychological, behavioural, and social determinants of suicide attempt and the remission of suicidal ideation, we are unlikely to see major gains in the prevention of suicide. AIM: The LifeTrack Project is a population-based longitudinal cohort study that aims to identify key modifiable risk and protective factors that predict the transition from suicidal ideation to suicide attempt or remission of suicidal ideation. We will assess theory-informed risk and protective factors using validated and efficient measures to identify distinct trajectories reflecting changes in severity of suicidal ideation and transition to suicide attempt over three years. METHODS: A three-year prospective population-based longitudinal cohort study will be conducted with adults from the general Australian population who initially report suicidal ideation (n = 842). Eligibility criteria include recent suicidal ideation (past 30 days), aged 18 years or older, living in Australia and fluent in English. Those with a suicide attempt in past 30 days or who are unable to participate in a long-term study will be excluded. Participants will be asked to complete online assessments related to psychopathology, cognition, psychological factors, social factors, mental health treatment use, and environmental exposures at baseline and every six months during this three-year period. One week of daily measurement bursts (ecological momentary assessments) at yearly intervals will also capture short-term fluctuations in suicidal ide
Published: 2023

14. Association of maternal and paternal perinatal depression and anxiety with infant development: A longitudinal study

Author: Rogers, AM, Youssef, GJ, Teague, S, Sunderland, M, Le Bas, G, Macdonald, JA, Mattick, RP, Allsop, S, Elliott, EJ, Olsson, CA, Hutchinson, D, Rogers, AM, Youssef, GJ, Teague, S, Sunderland, M, Le Bas, G, Macdonald, JA, Mattick, RP, Allsop, S, Elliott, EJ, Olsson, CA, and Hutchinson, D
Abstract: BACKGROUND: Maternal and paternal perinatal depression and anxiety are theorised to adversely impact infant development. Yet, few studies have assessed both mental health symptoms and clinical diagnoses within the one study. Moreover, research on fathers is limited. This study therefore aimed to examine the association between symptoms and diagnoses of maternal and paternal perinatal depression and anxiety with infant development. METHOD: Data were from the Triple B Pregnancy Cohort Study. Participants included 1539 mothers and 793 partners. Depressive and anxiety symptoms were assessed using the Edinburgh Postnatal Depression Scale and Depression Anxiety Stress Scales. Major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia were assessed using the Composite International Diagnostic Interview in trimester three. Infant development was assessed at 12-months using the Bayley Scales of Infant and Toddler Development. RESULTS: Antepartum, maternal depressive and anxiety symptoms were associated with poorer infant social-emotional (d = -0.11, p = .025) and language development (d = -0.16, p = .001). At 8-weeks postpartum, maternal anxiety symptoms were associated with poorer overall development (d = -0.11, p = .030). No association was observed for clinical diagnoses in mothers, nor paternal depressive and anxiety symptoms or clinical diagnoses; albeit risk estimates were largely in the expected direction of adverse effects on infant development. CONCLUSIONS: Evidence suggests that maternal perinatal depression and anxiety symptoms may adversely impact infant development. Effects were small but findings underscore the importance of prevention, early screening and intervention, alongside consideration of other risk factors during early critical periods.
Published: 2023

15. Prevalence of medical conditions, severity of IBS and asthma and associations with diet, other lifestyle behaviours and mental health in 5,015 Australian adolescents

Author: Osman, B., primary, Sunderland, M., additional, Jacka, F., additional, Thornton, L., additional, Teesson, M., additional, Moreno, L., additional, and Devine, E., additional
Published: 2023
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16. The relationship between alcohol use and dementia in adults aged more than 60 years: a combined analysis of prospective, individual-participant data from 15 international studies

Author: Mewton, L., Visontay, R., Hoy, N., Lipnicki, D. M., Sunderland, M., Lipton, R. B., Guerchet, M., Ritchie, K., Najar, J., Scarmeas, N., Kim, K.-W., Riedel Heller, S., Boxtel, M. van, Jacobsen, E., Brodaty, H., Anstey, K. J., Haan, M., Scazufca, M., Lobo, E., and Sachdev, P. S.
Abstract: Methods: Individual participant data meta-analysis of 15 prospective epidemiological cohort studies from countries situated in six continents. Cox regression investigated the dementia risk associated with alcohol use in older adults aged over 60 years. Additional analyses assessed the alcohol–dementia relationship in the sample stratified by sex and by continent. Participants included 24 478 community dwelling individuals without a history of dementia at baseline and at least one follow-up dementia assessment. The main outcome measure was all-cause dementia as determined by clinical interview. Results: At baseline, the mean age across studies was 71.8 (standard deviation = 7.5, range = 60–102 years), 14 260 (58.3%) were female and 13 269 (54.2%) were current drinkers. During 151 636 person-years of follow-up, there were 2124 incident cases of dementia (14.0 per 1000 person-years). When compared with abstainers, the risk for dementia was lower in occasional [hazard ratio (HR) = 0.78; 95% confidence interval (CI) = 0.68–0.89], light–moderate (HR = 0.78; 95% CI = 0.70–0.87) and moderate–heavy drinkers (HR = 0.62; 95% CI = 0.51–0.77). There was no evidence of differences between life-time abstainers and former drinkers in terms of dementia risk (HR = 0.98; 95% CI = 0.81–1.18). In dose–response analyses, moderate drinking up to 40 g/day was associated with a lower risk of dementia when compared with lif-time abstaining. Among current drinkers, there was no consistent evidence for differences in terms of dementia risk. Results were similar when the sample was stratified by sex. When analysed at the continent level, there was considerable heterogeneity in the alcohol–dementia relationship. Conclusions: Abstinence from alcohol appears to be associated with an increased risk for all-cause dementia. Among current drinkers, there appears to be no consistent evidence to suggest that the amount of alcohol consumed in later life is associated with dementia risk.
Published: 2023

17. Reductions in the internalising construct following internet-delivered treatment for anxiety and depression in primary care

Author: Mewton, L., Hobbs, M.J., Sunderland, M., Newby, J., and Andrews, G.
Published: 2014
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18. Unmet needs, quality of life and psychological distress: insights regarding head and neck cancer patients in a rural setting

Author: Sunderland, M, primary, Matthews, C, additional, Waterhouse, D, additional, Shetty, S, additional, and Morton, R P, additional
Published: 2022
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19. Lifestyle risks for chronic disease among Australian adolescents: a cross-sectional survey.

Author: Champion, KE, Chapman, C, Gardner, LA, Sunderland, M, Newton, NC, Smout, S, Thornton, LK, Hides, L, McBride, N, Allsop, SJ, Mills, K, Kay-Lambkin, F, Teesson, M, Slade, T, Heath4Life team, Champion, KE, Chapman, C, Gardner, LA, Sunderland, M, Newton, NC, Smout, S, Thornton, LK, Hides, L, McBride, N, Allsop, SJ, Mills, K, Kay-Lambkin, F, Teesson, M, Slade, T, and Heath4Life team
Published: 2022

20. Are there non-linear relationships between alcohol consumption and long-term health?: a systematic review of observational studies employing approaches to improve causal inference.

Author: Visontay, R, Sunderland, M, Slade, T, Wilson, J, Mewton, L, Visontay, R, Sunderland, M, Slade, T, Wilson, J, and Mewton, L
Abstract: BACKGROUND: Research has long found 'J-shaped' relationships between alcohol consumption and certain health outcomes, indicating a protective effect of moderate consumption. However, methodological limitations in most studies hinder causal inference. This review aimed to identify all observational studies employing improved approaches to mitigate confounding in characterizing alcohol-long-term health relationships, and to qualitatively synthesize their findings. METHODS: Eligible studies met the above description, were longitudinal (with pre-defined exceptions), discretized alcohol consumption, and were conducted with human populations. MEDLINE, PsycINFO, Embase and SCOPUS were searched in May 2020, yielding 16 published manuscripts reporting on cancer, diabetes, dementia, mental health, cardiovascular health, mortality, HIV seroconversion, and musculoskeletal health. Risk of bias of cohort studies was evaluated using the Newcastle-Ottawa Scale, and a recently developed tool was used for Mendelian Randomization studies. RESULTS: A variety of functional forms were found, including reverse J/J-shaped relationships for prostate cancer and related mortality, dementia risk, mental health, and certain lipids. However, most outcomes were only evaluated by a single study, and few studies provided information on the role of alcohol consumption pattern. CONCLUSIONS: More research employing enhanced causal inference methods is urgently required to accurately characterize alcohol-long-term health relationships. Those studies that have been conducted find a variety of linear and non-linear functional forms, with results tending to be discrepant even within specific health outcomes. TRIAL REGISTRATION: PROSPERO registration number CRD42020185861.
Published: 2022

21. Association of adolescent and young adult depression and anxiety with perinatal mental health in fathers: Findings from an Australian longitudinal study

Author: Lowrie, N, Le Bas, G, Youssef, G, Macdonald, JA, Teague, S, Rogers, A, Sunderland, M, Mattick, R, Elliott, EJ, Allsop, S, Burns, L, Najman, J, Jacobs, S, Olsson, CA, Hutchinson, D, Lowrie, N, Le Bas, G, Youssef, G, Macdonald, JA, Teague, S, Rogers, A, Sunderland, M, Mattick, R, Elliott, EJ, Allsop, S, Burns, L, Najman, J, Jacobs, S, Olsson, CA, and Hutchinson, D
Abstract: The current study examined associations between preconception diagnoses of major depressive disorder (MDD) and anxiety disorders in adolescence and young adulthood and perinatal depression and anxiety symptoms in early fatherhood. In an Australian community cohort study of health and development, earlier history of MDD and anxiety disorders (extending back to adolescence) were assessed retrospectively in the third trimester of pregnancy via the Composite International Diagnostic Interview. Paternal perinatal depression and anxiety were then assessed prospectively over three timepoints (third trimester of pregnancy, 8 weeks and 12 months postpartum), using established cut-points on the Edinburgh Postnatal Depression Scale and the Depression Anxiety Stress Scales (anxiety subscale). Mixed-effects regression models examined risk associations between preconception diagnoses of MDD and anxiety disorders, and perinatal depression and anxiety symptoms at each timepoint, adjusting for socio-demographic factors and concurrent maternal mental health difficulties. The odds of clinically concerning levels of paternal perinatal depression and anxiety were 6-fold and 4-fold higher, respectively, in men with a preconception history of MDD. The odds of perinatal depression were 3-fold higher in men with a preconception history of an anxiety disorder. Less evidence was found for an association between preconception diagnoses of an anxiety disorder and perinatal anxiety in fathers. Interventions aimed at improving mental health in men during adolescence and young adulthood may promote continued psychological health in men during early fatherhood.
Published: 2022

22. The structure of adolescent psychopathology: a symptom-level analysis

Author: Carragher, N., Teesson, M., Sunderland, M., Newton, N. C., Krueger, R. F., Conrod, P. J., Barrett, E. L., Champion, K. E., Nair, N. K., and Slade, T.
Published: 2016
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23. Unmet needs, quality of life and psychological distress: insights regarding head and neck cancer patients in a rural setting.

Author: Sunderland, M, Matthews, C, Waterhouse, D, Shetty, S, and Morton, R P
Subjects: *MENTAL depression risk factors, *RURAL conditions, *TRAVEL, *HEAD & neck cancer, *CANCER patients, *QUALITY of life, *QUESTIONNAIRES, *FINANCIAL stress, *DESCRIPTIVE statistics, *RESEARCH funding, *NEEDS assessment, *ANXIETY, *PSYCHOLOGICAL distress
Abstract: Objective: This study aimed to evaluate the perceived quality of life, unmet needs and psychological distress in patients with head and neck cancer in a rural setting in New Zealand. Method: Patients presenting with head and neck cancer in Northland, New Zealand, were asked to complete questionnaires on quality of life, unmet needs, and anxiety or depression together with a free-text option. Results: About one quarter of respondents (27 per cent) scored high in the anxiety and depression scale, with corresponding diminished quality of life scores and increased needs. Over half of respondents (54 per cent) found it challenging to travel for treatment. Financial difficulties were encountered more frequently with indigenous patients. Rurality alone does not lead to significant differences in quality of life or needs. Conclusion: After treatment for head and neck cancer, it is important to monitor and manage patients' psychological distress and ease of access to health services to improve quality of life. [ABSTRACT FROM AUTHOR]
Published: 2023
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24. Examining the shared and unique relationships among substance use and mental disorders

Author: Sunderland, M., Slade, T., and Krueger, R. F.
Published: 2015
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25. [Not Available].

Author: Krueger, RF, Kotov, R, Watson, D, Forbes, MK, Eaton, NR, Ruggero, CJ, Simms, LJ, Widiger, TA, Achenbach, TM, Bach, B, Bagby, RM, Bornovalova, MA, Carpenter, WT, Chmielewski, M, Cicero, DC, Clark, LA, Conway, C, DeClercq, B, DeYoung, CG, Docherty, AR, Drislane, LE, First, MB, Forbush, KT, Hallquist, M, Haltigan, JD, Hopwood, CJ, Ivanova, MY, Jonas, KG, Latzman, RD, Markon, KE, Miller, JD, Morey, LC, Mullins-Sweatt, SN, Ormel, J, Patalay, P, Patrick, CJ, Pincus, AL, Regier, DA, Reininghaus, U, Rescorla, LA, Samuel, DB, Sellbom, M, Shackman, AJ, Skodol, A, Slade, T, South, SC, Sunderland, M, Tackett, JL, Venables, NC, Waldman, ID, Waszczuk, MA, Waugh, MH, Wright, AGC, Zald, DH, Zimmermann, J, Krueger, RF, Kotov, R, Watson, D, Forbes, MK, Eaton, NR, Ruggero, CJ, Simms, LJ, Widiger, TA, Achenbach, TM, Bach, B, Bagby, RM, Bornovalova, MA, Carpenter, WT, Chmielewski, M, Cicero, DC, Clark, LA, Conway, C, DeClercq, B, DeYoung, CG, Docherty, AR, Drislane, LE, First, MB, Forbush, KT, Hallquist, M, Haltigan, JD, Hopwood, CJ, Ivanova, MY, Jonas, KG, Latzman, RD, Markon, KE, Miller, JD, Morey, LC, Mullins-Sweatt, SN, Ormel, J, Patalay, P, Patrick, CJ, Pincus, AL, Regier, DA, Reininghaus, U, Rescorla, LA, Samuel, DB, Sellbom, M, Shackman, AJ, Skodol, A, Slade, T, South, SC, Sunderland, M, Tackett, JL, Venables, NC, Waldman, ID, Waszczuk, MA, Waugh, MH, Wright, AGC, Zald, DH, and Zimmermann, J
Abstract: Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach.
Published: 2021

26. Characteristics of Early-Onset vs Late-Onset Colorectal Cancer A Review

Author: Zaborowski, AM, Abdile, A, Adamina, M, Aigner, F, d'Allens, L, Allmer, C, Alvarez, A, Anula, R, Andric, M, Atallah, S, Bach, S, Bala, M, Barussaud, M, Bausys, A, Bebington, B, Beggs, A, Bellolio, F, Bennett, M-R, Berdinskikh, A, Bevan, V, Biondo, S, Bislenghi, G, Bludau, M, Boutall, A, Brouwer, N, Brown, C, Bruns, C, Buchanan, DD, Buchwald, P, Burger, JWA, Burlov, N, Campanelli, M, Capdepont, M, Carvello, M, Chew, H-H, Christoforidis, D, Clark, D, Climent, M, Cologne, KG, Contreras, T, Croner, R, Daniels, IR, Dapri, G, Davies, J, Delrio, P, Denost, Q, Deutsch, M, Dias, A, D'Hoore, A, Drozdov, E, Duek, D, Dunlop, M, Dziki, A, Edmundson, A, Efetov, S, El-Hussuna, A, Elliot, B, Emile, S, Espin, E, Evans, M, Faes, S, Faiz, O, Fleming, F, Foppa, C, Fowler, G, Frasson, M, Figueiredo, N, Forgan, T, Frizelle, F, Gadaev, S, Gellona, J, Glyn, T, Gong, J, Goran, B, Greenwood, E, Guren, MG, Guillon, S, Gutlic, I, Hahnloser, D, Hampel, H, Hanly, A, Hasegawa, H, Iversen, LH, Hill, A, Hill, J, Hoch, J, Hoffmeister, M, Hompes, R, Hurtado, L, Iaquinandi, F, Imbrasaite, U, Islam, R, Jafari, MD, Kanemitsu, Y, Karachun, A, Karimuddin, AA, Keller, DS, Kelly, J, Kennelly, R, Khrykov, G, Kocian, P, Koh, C, Kok, N, Knight, KA, Knol, J, Kontovounisios, C, Korner, H, Krivokapic, Z, Kronberger, I, Kroon, HM, Kryzauskas, M, Kural, S, Kusters, M, Lakkis, Z, Lankov, T, Larson, D, Lazar, G, Lee, K-Y, Lee, SH, Lefevre, JH, Lepisto, A, Lieu, C, Loi, L, Lynch, C, Maillou-Martinaud, H, Maroli, A, Martin, S, Martling, A, Matzel, KE, Mayol, J, McDermott, F, Meurette, G, Millan, M, Mitteregger, M, Moiseenko, A, Monson, JRT, Morarasu, S, Moritani, K, Moslein, G, Munini, M, Nahas, C, Nahas, S, Negoi, I, Novikova, A, Ocares, M, Okabayashi, K, Olkina, A, Onate-Ocana, L, Otero, J, Ozen, C, Pace, U, Juliao, GPS, Panaiotti, L, Panis, Y, Papamichael, D, Park, J, Patel, S, Uriburu, JCP, Pera, M, Perez, RO, Petrov, A, Pfeffer, F, Phang, PT, Poskus, T, Pringle, H, Proud, D, Raguz, I, Rama, N, Rasheed, S, Raval, MJ, Rega, D, Reissfelder, C, Meneses, JCR, Ris, F, Riss, S, Rodriguez-Zentner, H, Roxburgh, CS, Saklani, A, Salido, AJ, Sammour, T, Saraste, D, Schneider, M, Seishima, R, Sekulic, A, Seppala, T, Sheahan, K, Shine, R, Shlomina, A, Sica, GS, Singnomklao, T, Siragusa, L, Smart, N, Solis, A, Spinelli, A, Staiger, RD, Stamos, MJ, Steele, S, Sunderland, M, Tan, K-K, Tanis, PJ, Tekkis, P, Teklay, B, Tengku, S, Jimenez-Toscano, M, Tsarkov, P, Turina, M, Ulrich, A, Vailati, BB, van Harten, M, Verhoef, C, Warrier, S, Wexner, S, de Wilt, H, Weinberg, BA, Wells, C, Wolthuis, A, Xynos, E, You, N, Zakharenko, A, Zeballos, J, Winter, DC, Zaborowski, AM, Abdile, A, Adamina, M, Aigner, F, d'Allens, L, Allmer, C, Alvarez, A, Anula, R, Andric, M, Atallah, S, Bach, S, Bala, M, Barussaud, M, Bausys, A, Bebington, B, Beggs, A, Bellolio, F, Bennett, M-R, Berdinskikh, A, Bevan, V, Biondo, S, Bislenghi, G, Bludau, M, Boutall, A, Brouwer, N, Brown, C, Bruns, C, Buchanan, DD, Buchwald, P, Burger, JWA, Burlov, N, Campanelli, M, Capdepont, M, Carvello, M, Chew, H-H, Christoforidis, D, Clark, D, Climent, M, Cologne, KG, Contreras, T, Croner, R, Daniels, IR, Dapri, G, Davies, J, Delrio, P, Denost, Q, Deutsch, M, Dias, A, D'Hoore, A, Drozdov, E, Duek, D, Dunlop, M, Dziki, A, Edmundson, A, Efetov, S, El-Hussuna, A, Elliot, B, Emile, S, Espin, E, Evans, M, Faes, S, Faiz, O, Fleming, F, Foppa, C, Fowler, G, Frasson, M, Figueiredo, N, Forgan, T, Frizelle, F, Gadaev, S, Gellona, J, Glyn, T, Gong, J, Goran, B, Greenwood, E, Guren, MG, Guillon, S, Gutlic, I, Hahnloser, D, Hampel, H, Hanly, A, Hasegawa, H, Iversen, LH, Hill, A, Hill, J, Hoch, J, Hoffmeister, M, Hompes, R, Hurtado, L, Iaquinandi, F, Imbrasaite, U, Islam, R, Jafari, MD, Kanemitsu, Y, Karachun, A, Karimuddin, AA, Keller, DS, Kelly, J, Kennelly, R, Khrykov, G, Kocian, P, Koh, C, Kok, N, Knight, KA, Knol, J, Kontovounisios, C, Korner, H, Krivokapic, Z, Kronberger, I, Kroon, HM, Kryzauskas, M, Kural, S, Kusters, M, Lakkis, Z, Lankov, T, Larson, D, Lazar, G, Lee, K-Y, Lee, SH, Lefevre, JH, Lepisto, A, Lieu, C, Loi, L, Lynch, C, Maillou-Martinaud, H, Maroli, A, Martin, S, Martling, A, Matzel, KE, Mayol, J, McDermott, F, Meurette, G, Millan, M, Mitteregger, M, Moiseenko, A, Monson, JRT, Morarasu, S, Moritani, K, Moslein, G, Munini, M, Nahas, C, Nahas, S, Negoi, I, Novikova, A, Ocares, M, Okabayashi, K, Olkina, A, Onate-Ocana, L, Otero, J, Ozen, C, Pace, U, Juliao, GPS, Panaiotti, L, Panis, Y, Papamichael, D, Park, J, Patel, S, Uriburu, JCP, Pera, M, Perez, RO, Petrov, A, Pfeffer, F, Phang, PT, Poskus, T, Pringle, H, Proud, D, Raguz, I, Rama, N, Rasheed, S, Raval, MJ, Rega, D, Reissfelder, C, Meneses, JCR, Ris, F, Riss, S, Rodriguez-Zentner, H, Roxburgh, CS, Saklani, A, Salido, AJ, Sammour, T, Saraste, D, Schneider, M, Seishima, R, Sekulic, A, Seppala, T, Sheahan, K, Shine, R, Shlomina, A, Sica, GS, Singnomklao, T, Siragusa, L, Smart, N, Solis, A, Spinelli, A, Staiger, RD, Stamos, MJ, Steele, S, Sunderland, M, Tan, K-K, Tanis, PJ, Tekkis, P, Teklay, B, Tengku, S, Jimenez-Toscano, M, Tsarkov, P, Turina, M, Ulrich, A, Vailati, BB, van Harten, M, Verhoef, C, Warrier, S, Wexner, S, de Wilt, H, Weinberg, BA, Wells, C, Wolthuis, A, Xynos, E, You, N, Zakharenko, A, Zeballos, J, and Winter, DC
Abstract: IMPORTANCE: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. OBSERVATIONS: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. CONCLUSIONS AND RELEVANCE: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.
Published: 2021

27. A detailed hierarchical model of psychopathology: From individual symptoms up to the general factor of psychopathology.

Author: Forbes, MK, Sunderland, M, Rapee, RM, Batterham, PJ, Calear, AL, Carragher, N, Ruggero, C, Zimmerman, M, Baillie, AJ, Lynch, SJ, Mewton, L, Slade, T, Krueger, RF, Forbes, MK, Sunderland, M, Rapee, RM, Batterham, PJ, Calear, AL, Carragher, N, Ruggero, C, Zimmerman, M, Baillie, AJ, Lynch, SJ, Mewton, L, Slade, T, and Krueger, RF
Abstract: Much of our knowledge about the relationships among domains of psychopathology is built on the diagnostic categories described in the Diagnostic and Statistical Manual of Mental Disorders (DSM), with relatively little research examining the symptom-level structure of psychopathology. The aim of this study was to delineate a detailed hierarchical model of psychopathology-from individual symptoms up to a general factor of psychopathology-allowing both higher- and lower-order dimensions to depart from the structure of the DSM. We explored the hierarchical structure of hundreds of symptoms spanning 18 DSM disorders, in two large samples-one from the general population in Australia (n = 3175), and the other a treatment-seeking clinical sample from the USA (n = 1775). There was marked convergence between the two samples, offering new perspectives on higher-order dimensions of psychopathology. We also found several noteworthy departures from the structure of the DSM in the symptom-level data.
Published: 2021

28. Are there non-linear relationships between alcohol consumption and long-term health? Protocol for a systematic review of observational studies employing approaches to improve causal inference.

Author: Visontay, R, Sunderland, M, Slade, T, Wilson, J, Mewton, L, Visontay, R, Sunderland, M, Slade, T, Wilson, J, and Mewton, L
Abstract: INTRODUCTION: There is a substantial literature finding that moderate alcohol consumption is protective against certain health conditions. However, more recent research has highlighted the possibility that these findings are methodological artefacts, caused by confounding and other biases. While modern analytical and study design approaches can mitigate confounding and thus enhance causal inference in observational studies, they are not routinely applied in research assessing the relationship between alcohol use and long-term health outcomes. The purpose of this systematic review is to identify observational studies that employ these analytical/design-based approaches in assessing whether relationships between alcohol consumption and health outcomes are non-linear. This review seeks to evaluate, on a per-outcome basis, what these studies find the strength and form of the relationship between alcohol consumption and health to be. METHODS AND ANALYSIS: Electronic databases (MEDLINE, PsycINFO, Embase and SCOPUS) were searched in May 2020. Study selection will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles will be screened against eligibility criteria intended to capture studies using observational data to assess the relationship between varying levels of alcohol exposure and any long-term health outcome (actual or surrogate), and that have employed at least one of the prespecified approaches to enhancing causal inference. Risk of bias of included articles will be assessed using study design-specific tools. A narrative synthesis of the results is planned. ETHICS AND DISSEMINATION: Formal ethics approval is not required given there will be no primary data collection. The results of the study will be disseminated through published manuscripts, conferences and seminar presentations. PROSPERO REGISTRATION NUMBER: CRD42020185861.
Published: 2021

29. An examination of generalized anxiety disorder and dysthymic disorder by latent class analysis

Author: Rhebergen, D., van der Steenstraten, I. M., Sunderland, M., de Graaf, R., ten Have, M., Lamers, F., Penninx, B. W. J. H., and Andrews, G.
Published: 2014

30. Reflections on the Shifting Shape of Journalism Education in the Covid-19 pandemic

Author: Fowler-Watt, Karen, Majin, G., Sunderland, M., Phillips, Miriam, Brine, David, Bissell, Andrew, and Murphy, Jaron
Abstract: Journalists usually report on crisis. The Covid -19 pandemic places journalists, like everyone else, in the crisis. Thus, it presents a unique challenge to journalism, which is founded on the principle of impartiality, and to journalism educators, striving to teach professional values in an online environment, whilst also focusing on student wellbeing. This paper shares the initial reflections of journalism practitioners who are members of a journalism education research group within the Centre for Excellence in Media Practice at Bournemouth University in the UK. The overarching theme considers the delivery of high quality, industry - facing and relevant journalism education in a digital environment and within a context where we are all part of the story. We reflect on building community and identity for undergraduate and postgraduate students; the challenges of teaching the normative values and skills of journalism (such as objectivity, accuracy, fairness), emotional literacy and the delivery of industry-accredited standards. These individual reflections are presented as a collective essay which engages with questions of identity, self and voice: how can we instil a sense of wellbeing in journalism students who may feel anxious and marginalised? How can they focus on telling the stories of others when they are part of the same story? How can we best engage with these challenges in a digital environment, whilst instilling an understanding of the importance of self–care and wellbeing? In responding and adapting to crisis, we have also discovered - through the work of our students in the virtual classroom - new ways of teaching journalism and innovative approaches to storytelling as we grapple together with the shifting shapes of journalism practice and journalism education.
Published: 2020

31. Clustering of six key risk behaviors for chronic disease among adolescent females

Author: Gardner, LA, Champion, KE, Parmenter, B, Grummitt, L, Chapman, C, Sunderland, M, Thornton, L, McBride, N, Newton, NC, Gardner, LA, Champion, KE, Parmenter, B, Grummitt, L, Chapman, C, Sunderland, M, Thornton, L, McBride, N, and Newton, NC
Abstract: Chronic diseases are the leading cause of disability and mortality globally. In Australia, females are at heightened risk. This research explored the prevalence, patterns, and correlates of six key risk behaviors (physical inactivity, poor diet, recreational screen time, inadequate sleep, alcohol use, and smoking) among adolescent females and whether knowledge of health guidelines was associated with adherence. Adolescent females completed an anonymous online questionnaire (N = 687; Mage = 13.82). Logistic regression assessed the association between knowledge and adherence. A Latent Class Analysis (LCA) and three-step procedure identified risk behavior clusters and their correlates. Despite positive health self-ratings (77% good/very good), most participants reported insufficient moderate-to-vigorous physical activity (MVPA; 89%), vegetable intake (89%), and excessive screen time (63%). Knowledge of guidelines was associated with adherence for MVPA, vegetable intake, sleep, and alcohol abstinence. Three classes emerged: “moderate risk” (76%), “relatively active, healthy eaters” (19%), and “excessive screen users” (5%). These risk-behavior clusters were associated with perceived value of academic achievement and physical wellbeing. Adolescent females commonly perceive they are in good health, despite engaging in unhealthy behaviors. Public health interventions should utilize effective behavior change strategies, adopt a multiple health behavior change approach (MHBC), and be tailored to specific risk profiles and values among females.
Published: 2020

32. Study protocol of the Health4Life initiative: A cluster randomised controlled trial of an eHealth school-based program targeting multiple lifestyle risk behaviours among young Australians

Author: Teesson, M, Champion, KE, Newton, NC, Kay-Lambkin, F, Chapman, C, Thornton, L, Slade, T, Sunderland, M, Mills, K, Gardner, LA, Parmenter, B, Lubans, DR, Hides, L, McBride, N, Allsop, S, Spring, BJ, Smout, S, Osman, B, Teesson, M, Champion, KE, Newton, NC, Kay-Lambkin, F, Chapman, C, Thornton, L, Slade, T, Sunderland, M, Mills, K, Gardner, LA, Parmenter, B, Lubans, DR, Hides, L, McBride, N, Allsop, S, Spring, BJ, Smout, S, and Osman, B
Abstract: Introduction Lifestyle risk behaviours, including alcohol use, smoking, poor diet, physical inactivity, poor sleep (duration and/or quality) and sedentary recreational screen time ( € the Big 6'), are strong determinants of chronic disease. These behaviours often emerge during adolescence and co-occur. School-based interventions have the potential to address risk factors prior to the onset of disease, yet few eHealth school-based interventions target multiple behaviours concurrently. This paper describes the protocol of the Health4Life Initiative, an eHealth school-based intervention that concurrently addresses the Big 6 risk behaviours among secondary school students. Methods and analysis A multisite cluster randomised controlled trial will be conducted among year 7 students (11-13 years old) from 72 Australian schools. Stratified block randomisation will be used to assign schools to either the Health4Life intervention or an active control (health education as usual). Health4Life consists of (1) six web-based cartoon modules and accompanying activities delivered during health education (once per week for 6 weeks), and a smartphone application (universal prevention), and (2) additional app content, for students engaging in two or more risk behaviours when they are in years 8 and 9 (selective prevention). Students will complete online self-report questionnaires at baseline, post intervention, and 12, 24 and 36 months after baseline. Primary outcomes are consumption of sugar-sweetened beverages, moderate-to-vigorous physical activity, sleep duration, sedentary recreational screen time and uptake of alcohol and tobacco use. Ethics and dissemination This study has been approved by the University of Sydney (2018/882), NSW Department of Education (SERAP no. 2019006), University of Queensland (2019000037), Curtin University (HRE2019-0083) and relevant Catholic school committees. Results will be presented to schools and findings disseminated via peer-reviewed journals and s
Published: 2020

33. Measurement properties of smartphone approaches to assess key lifestyle behaviours: Protocol of a systematic review

Author: Thornton, L, Osman, B, Wescott, AB, Sunderland, M, Champion, K, Green, O, Kay-Lambkin, F, Slade, T, Newton, N, Chapman, C, Teesson, M, Mills, K, Birrell, L, Lubans, D, Van De Ven, P, Torous, J, Parmenter, B, Gardner, L, Thornton, L, Osman, B, Wescott, AB, Sunderland, M, Champion, K, Green, O, Kay-Lambkin, F, Slade, T, Newton, N, Chapman, C, Teesson, M, Mills, K, Birrell, L, Lubans, D, Van De Ven, P, Torous, J, Parmenter, B, and Gardner, L
Abstract: Background: Six core behavioural risk factors (poor diet, physical activity, sedentary behaviour, alcohol misuse, smoking and unhealthy sleep patterns) have been identified as strong determinants of chronic disease, such as cardiovascular disease, diabetes and cancers. Smartphones have the potential to provide a real-time, pervasive, unobtrusive and cost-effective way to measure health behaviours and deliver instant feedback to users. Despite this, validity of using smartphones to measure these six key behaviours is largely unknown. The proposed systematic review aims to address this gap by identifying existing smartphone-based approaches to measure these health behaviours and critically appraising, comparing and summarizing the quality of their measurement properties. Methods: A systematic search of the Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsychINFO (EBSCOhost), CINAHL (EBSCOHost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost) and IEEE Xplore Digital Library databases will be conducted from January 2007 to March 2020. Eligible studies will be those written in English that measure at least one of the six health behaviours of interest via a smartphone and report on at least one measurement property. The primary outcomes will be validity, reliability and/or responsiveness of these measurement approaches. A secondary outcome will be the feasibility (e.g. user burden, usability and cost) of identified approaches. No restrictions will be placed on the participant population or study design. Two reviewers will independently screen studies for eligibility, extract data and assess the risk of bias. The study methodological quality (or bias) will be appraised using an appropriate tool. Our results will be described in a narrative synthesis. If feasible, random effects meta-analysis will be conducted where appropriate. Discussion: The results from this review will provide important information about the types of smartphone-based approaches currentl
Published: 2020

34. Limitations in knowledge and practice of healthy lifestyle guidelines in a sample of Australian adults.

Author: Parmenter, B, Gardner, L, Champion, K, Chapman, C, Thornton, L, McBride, N, Sunderland, M, Newton, N, Parmenter, B, Gardner, L, Champion, K, Chapman, C, Thornton, L, McBride, N, Sunderland, M, and Newton, N
Published: 2020

35. Psychotic-like experiences in a community sample of 8000 children aged 9 to 11 years: an item response theory analysis

Author: Laurens, K. R., Hobbs, M. J., Sunderland, M., Green, M. J., and Mould, G. L.
Published: 2012

36. Investigating differential symptom profiles in major depressive episode with and without generalized anxiety disorder: true co-morbidity or symptom similarity?

Author: Sunderland, M., Mewton, L., Slade, T., and Baillie, A. J.
Published: 2010

37. Neurodevelopmental disorders: Cluster 2 of the proposed meta-structure for DSM-V and ICD-11. Paper 3 of 7 of the thematic section: ‘A proposal for a meta-structure for DSM-V and ICD-11’

Author: Andrews, G., Pine, D. S., Hobbs, M. J., Anderson, T. M., and Sunderland, M.
Published: 2009

38. Neurocognitive disorders: Cluster 1 of the proposed meta-structure for DSM-V and ICD-11. Paper 2 of 7 of the thematic section: ‘A proposal for a meta-structure for DSM-V and ICD-11’

Author: Sachdev, P., Andrews, G., Hobbs, M. J., Sunderland, M., and Anderson, T. M.
Published: 2009

39. CLASSIFICATION OF ANXIETY AND DEPRESSIVE DISORDERS: PROBLEMS AND SOLUTIONS

Author: Andrews, G., Anderson, T. M., Slade, T., Sunderland, M., and Psychol, B
Published: 2008
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40. An eHealth multiple health behavior change intervention for school students: Development and Protocol of Health4Life.

Author: Champion, K, Newton, N, Kay-Lambkin, F, Thornton, L, Slade, T, Mills, K, Sunderland, M, Gardner, L, Parmenter, B, Lubans, D, Hides, L, McBride, N, Allsop, S, Spring, B, Smout, S, Osman, B, Teesson, M, Champion, K, Newton, N, Kay-Lambkin, F, Thornton, L, Slade, T, Mills, K, Sunderland, M, Gardner, L, Parmenter, B, Lubans, D, Hides, L, McBride, N, Allsop, S, Spring, B, Smout, S, Osman, B, and Teesson, M
Published: 2019

41. Key Considerations in Planning for Substance Use Treatment: Estimating Treatment Need and Demand

Author: Ritter, A, Mellor, R, Chalmers, J, Sunderland, M, Lancaster, K, Ritter, A, Mellor, R, Chalmers, J, Sunderland, M, and Lancaster, K
Abstract: OBJECTIVE: Estimates of the extent of treatment need (defined by the presence of a diagnosis for which there is an effective treatment available) and treatment demand (defined as treatment seeking) are essential parts of effective treatment planning, service provision, and treatment funding. This article reviews the existing literature on approaches to estimating need and demand and the use of models to inform such estimation, and then considers the implications for health planners. METHOD: A thematic review of the literature was undertaken, with a focus on covering the key concepts and research methods that have been used to date. RESULTS: Both need and demand are important estimates in planning for services but contain many difficulties in moving from the theory of measurement to the practicalities of establishing these figures. Furthermore, the simple quantum of need or demand is limited in its usefulness unless it is matched with consideration of different treatment types and their relative intensity, and/or explored as a function of geography and subpopulation. Modeling can assist with establishing more fine-tuned planning estimates, and is able to take into account both client severity and the various treatment types that might be available. CONCLUSIONS: Moving from relatively simplistic estimates of need and demand for treatment, this review has shown that although such estimation can inform national or subnational treatment planning, more sophisticated models are required for alcohol and other drug treatment planning. These can help health planners to determine the appropriate amount and mix of treatments for substance use disorders.
Published: 2019

42. AN EHEALTH MULTIPLE HEALTH BEHAVIOR CHANGE INTERVENTION FOR SCHOOL STUDENTS: DEVELOPMENT AND PROTOCOL OF HEALTH4LIFE

Author: McGowan, C, Champion, K, Newton, N, Kay-Lambkin, F, Chapman, C, Thornton, LK, Slade, T, Mills, K, Sunderland, M, Allsop, SJ, Hides, L, McBride, N, Bauer, J, Parmenter, BJ, Spring, B, Lubans, DR, Gardner, LA, Teesson, M, McGowan, C, Champion, K, Newton, N, Kay-Lambkin, F, Chapman, C, Thornton, LK, Slade, T, Mills, K, Sunderland, M, Allsop, SJ, Hides, L, McBride, N, Bauer, J, Parmenter, BJ, Spring, B, Lubans, DR, Gardner, LA, and Teesson, M
Published: 2019

43. Patterns and prevalence of the “big 6”: Behavioural risk factors for chronic disease among Australian adolescent females

Author: Gardner, L, Champion, K, Newton, N, Chapman, C, Thornton, L, Sunderland, M, Parmenter, B, McGowan, C, Teesson, M, Gardner, L, Champion, K, Newton, N, Chapman, C, Thornton, L, Sunderland, M, Parmenter, B, McGowan, C, and Teesson, M
Published: 2019

44. Effectiveness of school-based eHealth interventions to prevent multiple lifestyle risk behaviours among adolescents: a systematic review and meta-analysis

Author: Champion, KE, Parmenter, B, McGowan, C, Spring, B, Wafford, QE, Gardner, LA, Thornton, L, McBride, N, Barrett, EL, Teesson, M, Newton, NC, Chapman, C, Slade, T, Sunderland, M, Bauer, J, Allsop, S, Hides, L, Stapinksi, L, Birrell, L, Mewton, L, Champion, KE, Parmenter, B, McGowan, C, Spring, B, Wafford, QE, Gardner, LA, Thornton, L, McBride, N, Barrett, EL, Teesson, M, Newton, NC, Chapman, C, Slade, T, Sunderland, M, Bauer, J, Allsop, S, Hides, L, Stapinksi, L, Birrell, L, and Mewton, L
Abstract: Background: Lifestyle risk behaviours typically emerge during adolescence, track into adulthood, and commonly co-occur. Interventions targeting multiple risk behaviours in adolescents have the potential to efficiently improve health outcomes, yet further evidence is required to determine their effect. We reviewed the effectiveness of eHealth school-based interventions targeting multiple lifestyle risk behaviours. Methods: In this systematic review and meta-analysis, we searched Ovid MEDLINE, Embase, PsycINFO, and the Cochrane Library databases between Jan 1, 2000, and March 14, 2019, with no language restrictions, for publications on school-based eHealth multiple health behaviour interventions in humans. We also screened the grey literature for unpublished data. Eligible studies were randomised controlled trials of eHealth (internet, computers, tablets, mobile technology, or tele-health) interventions targeting two or more of six behaviours of interest: alcohol use, smoking, diet, physical activity, sedentary behaviour, and sleep. Primary outcomes of interest were the prevention or reduction of unhealthy behaviours, or improvement in healthy behaviours of the six behaviours. Outcomes were summarised in a narrative synthesis and combined using random-effects meta-analysis. This systematic review is registered with PROSPERO, identifier CRD42017072163. Findings: Of 10 571 identified records, 22 publications assessing 16 interventions were included, comprising 18 873 students, of whom on average 56·2% were female, with a mean age of 13·41 years (SD 1·52). eHealth school-based multiple health behaviour change interventions significantly increased fruit and vegetable intake (standard mean difference 0·11, 95% CI 0·03 to 0·19; p=0·007) and both accelerometer-measured (0·33, 0·05 to 0·61; p=0·02) and self-reported (0·14, 0·05 to 0·23; p=0·003) physical activity, and reduced screen time (−0·09, −0·17 to −0·01; p=0·03) immediately after the intervention; however, these effect
Published: 2019

45. Psychometric Properties of 7- and 30-Day Versions of the PROMIS Emotional Distress Item Banks in an Australian Adult Sample

Author: Batterham, PJ, Sunderland, M, Carragher, N, Calear, AL, Batterham, PJ, Sunderland, M, Carragher, N, and Calear, AL
Abstract: This study aimed to examine the psychometric properties of the PROMIS depression, anxiety, and anger item banks in a large Australian population-based sample. The study tested for unidimensionality; evaluated invariance across age, gender, and education; assessed local independence; and tested item bank scores as an indicator for clinical criteria. In addition, equivalence of the 7-day time frame against an alternative 30-day time frame was assessed. A sample of 3,175 Australian adults were recruited into the study through online advertising. All three item banks showed strong evidence of unidimensionality and parsimony, with no items showing local dependence. All items were invariant across age, gender, and education. The item banks were accurate in detecting clinical criteria for major depressive disorder, generalized anxiety disorder, and panic disorder, although legacy measures designed for this purpose sometimes performed marginally better. Responses to the 30-day time frame were highly consistent with the original 7-day time frame. The study provided support for the validity of the PROMIS emotional distress item banks as measures of depression, anxiety, and anger in the Australian population, supporting the generalizability of the measures. The time frame chosen for assessing mental health outcomes using these item banks should be based on pragmatic considerations.
Published: 2019

46. Independent Effects of Mental Disorders on Suicidal Behavior in the Community

Author: Batterham, PJ, Calear, AL, Christensen, H, Carragher, N, Sunderland, M, Batterham, PJ, Calear, AL, Christensen, H, Carragher, N, and Sunderland, M
Abstract: This study assessed the independent contributions of nine common mental disorders on suicide ideation and suicide attempt. A community-based survey of Australian adults (N = 3,175) was conducted to identify common mental disorders associated with recent suicide attempt. Nine disorders were assessed using DSM-5 clinical criteria. Logistic regression models indicated that all disorders were significantly and independently associated with suicide ideation. However, only obsessive-compulsive disorder and posttraumatic stress disorder were significantly associated with suicide attempt among participants with ideation, independently of other disorders (OR = 2.0 for both). Increasing comorbidity had a significant monotonic association with suicide ideation but not attempts.
Published: 2018

47. Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

Author: Arce Vargas, F, Furness, AJS, Solomon, I, Joshi, K, Mekkaoui, L, Lesko, MH, Miranda Rota, E, Dahan, R, Georgiou, A, Sledzinska, A, Ben Aissa, A, Franz, D, Werner Sunderland, M, Wong, YNS, Henry, JY, O'Brien, T, Nicol, D, Challacombe, B, Beers, SA, Spain, L, Wotherspoon, A, Francis, N, Smith, M, Strauss, D, Hayes, A, Soultati, A, Stares, M, Lynch, J, Fotiadis, N, Fernando, A, Hazell, S, Chandra, A, Pickering, L, Rudman, S, Chowdhury, S, Swanton, C, Jamal-Hanjani, M, Veeriah, S, Shafi, S, Czyzewska-Khan, J, Johnson, D, Laycock, J, Bosshard-Carter, L, Goh, G, Rosenthal, R, Gorman, P, Murugaesu, N, Hynds, RE, Wilson, G, Birkbak, NJ, Watkins, TBK, McGranahan, N, Horswell, S, Mitter, R, Escudero, M, Stewart, A, Van Loo, P, Rowan, A, Xu, H, Turajlic, S, Hiley, C, Abbosh, C, Goldman, J, Stone, RK, Denner, T, Matthews, N, Elgar, G, Ward, S, Biggs, J, Costa, M, Begum, S, Phillimore, B, Chambers, T, Nye, E, Graca, S, Al Bakir, M, Hartley, JA, Lowe, HL, Herrero, J, Lawrence, D, Hayward, M, Panagiotopoulos, N, Kolvekar, S, Falzon, M, and Borg, E
Subjects: hemic and immune systems, chemical and pharmacologic phenomena
Abstract: CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.
Published: 2017

48. Use of post mortem vitreous humour electrolytes in diagnosing salt water drowning deaths

Author: Garland, Jack, primary, Tse, Rexson, additional, Anne, S., additional, Oldmeadow, C., additional, Attia, J., additional, Vilain, R., additional, Elstub, H., additional, Kesha, K., additional, Stables, S., additional, Kuo, T., additional, Sunderland, M., additional, Garland, S., additional, Lam, L., additional, and Cala, Allan, additional
Published: 2018
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49. Deciphering the intra-tumoural T cell receptor repertoire in patients with NSCLC within the lung TRACERx study

Author: Joshi, K., primary, Reading, J.L., additional, Ismail, M., additional, Oakes, T., additional, Rosenthal, R., additional, Uddin, I., additional, Jamal-Hanjani, M., additional, McGranahan, N., additional, Wong, Y.N.S., additional, Furness, A.J., additional, Aissa, A.B., additional, Werner Sunderland, M., additional, Georgiou, A., additional, Veeriah, S., additional, Czyzewska-Khan, J., additional, Marafioti, T., additional, Peggs, K., additional, Swanton, C., additional, Chain, B.M., additional, and Quezada, S., additional
Published: 2017
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50. Efficiently measuring dimensions of the externalizing spectrum model: Development of the externalizing spectrum inventory-computerized adaptive test (ESI-CAT)

Author: Sunderland, M, Slade, T, Krueger, RF, Markon, KE, Patrick, CJ, Kramer, MD, Sunderland, M, Slade, T, Krueger, RF, Markon, KE, Patrick, CJ, and Kramer, MD
Abstract: The development of the Externalizing Spectrum Inventory (ESI) was motivated by the need to comprehensively assess the interrelated nature of externalizing psychopathology and personality using an empirically driven framework. The ESI measures 23 theoretically distinct yet related unidimensional facets of externalizing, which are structured under 3 superordinate factors representing general externalizing, callous aggression, and substance abuse. One limitation of the ESI is its length at 415 items. To facilitate the use of the ESI in busy clinical and research settings, the current study sought to examine the efficiency and accuracy of a computerized adaptive version of the ESI. Data were collected over 3 waves and totaled 1,787 participants recruited from undergraduate psychology courses as well as male and female state prisons. A series of 6 algorithms with different termination rules were simulated to determine the efficiency and accuracy of each test under 3 different assumed distributions. Scores generated using an optimal adaptive algorithm evidenced high correlations (r > .9) with scores generated using the full ESI, brief ESI item-based factor scales, and the 23 facet scales. The adaptive algorithms for each facet administered a combined average of 115 items, a 72% decrease in comparison to the full ESI. Similarly, scores on the item-based factor scales of the ESI-brief form (57 items) were generated using on average of 17 items, a 70% decrease. The current study successfully demonstrates that an adaptive algorithm can generate similar scores for the ESI and the 3 item-based factor scales using a fraction of the total item pool.
Published: 2017

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