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

Author

Al-Sawaf, Othman, Weiss, Jakob, Skrzypski, Marcin, Lam, Jie Min, Karasaki, Takahiro, Zambrana, Francisco, Kidd, Andrew C, Frankell, Alexander M, Watkins, Thomas BK, Martinez-Ruiz, Carlos, Puttick, Clare, Black, James RM, Huebner, Ariana, Al Bakir, Maise, Sokac, Mateo, Collins, Susie, Veeriah, Selvaraju, Magno, Neil, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Ward, Sophia, Jayanth, Nick, Salgado, Roberto, Bridge, Christopher P, Christiani, David C, Mak, Raymond H, Bay, Camden, Rosenthal, Michael, Sattar, Naveed, Welsh, Paul, Liu, Ying, Perrimon, Norbert, Popuri, Karteek, Beg, Mirza Faisal, McGranahan, Nicholas, Hackshaw, Allan, Breen, Danna M, O'Rahilly, Stephen, Birkbak, Nicolai J, Aerts, Hugo JWL, Jamal-Hanjani, Mariam, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Van Loo, Peter, Szallasi, Zoltan, Kisistok, Judit, Diossy, Miklos, Demeulemeester, Jonas, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Abbosh, Christopher, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Hiley, Crispin T, Moore, David A, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Cadieux, Elizabeth Larose, Lim, Emilia L, Colliver, Emma, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Hartley, John A, Peggs, Karl S, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Grigoriadis, Kristiana, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Hill, Mark S, Dietzen, Michelle, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Pich, Oriol, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Zaccaria, Simone, Hessey, Sonya, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Male, Proteomics, Cachexia, Lung Neoplasms, Antigens, Neoplasm, Carcinoma, Non-Small-Cell Lung, Body Weight, Body Composition, Humans, Neoplasm Recurrence, Local, Muscle, Skeletal, Neoplasm Proteins
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. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

2. The evolution of non-small cell lung cancer metastases in TRACERx

Author

Al Bakir, Maise, Huebner, Ariana, Martinez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas BK, Pich, Oriol, Moore, David A, Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander, Bunkum, Abigail, Lim, Emilia L, Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T, Hill, Mark S, Cook, Daniel E, Wilson, Gareth A, Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R, Blackhall, Fiona H, Cave, Judith, Blyth, Kevin G, Nair, Arjun, Ahmed, Asia, Taylor, Magali N, Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Papadatos-Pastos, Dionysis, Forster, Martin D, Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio, Peggs, Karl S, Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Benafif, Sarah, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Krebs, Matthew G, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Puttick, Clare, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Black, James RM, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Clonal Evolution, Cohort Studies, Evolution, Molecular, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Disease Progression, Humans, Neoplasm Metastasis, Neoplasm Recurrence, Local, Clone Cells
Abstract

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

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

Author

Frankell, Alexander M, Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L, Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S, Grigoriadis, Kristiana, Moore, David A, Black, James RM, Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas BK, Naceur-Lombardelli, Cristina, Cook, Daniel E, Salgado, Roberto, Wilson, Gareth A, Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martinez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G, Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Blyth, Kevin G, Fennell, Dean A, Forster, Martin D, Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J, Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G, Lester, Jason F, Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M, Lawrence, David, Navani, Neal, Janes, Sam M, Dive, Caroline, Blackhall, Fiona H, Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A, Peggs, Karl S, Schwarz, Roland F, Van Loo, Peter, Miedema, Daniel M, Birkbak, Nicolai J, Hiley, Crispin T, Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joa, Primrose, Lindsay, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Kaufmann, Tom L, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran L, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Rane, Jayant K, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Danson, Sarah, Robinson, Lily, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Lung Neoplasms, Treatment Outcome, DNA Copy Number Variations, Mutagenesis, Carcinoma, Non-Small-Cell Lung, Mutation, Smoking, Humans, Adenocarcinoma of Lung, Neoplasm Recurrence, Local, Phylogeny
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. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

4. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author

Karasaki, Takahiro, Moore, David A, Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Al Bakir, Maise, Watkins, Thomas BK, Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S, Frankell, Alexander M, Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L, Martinez-Ruiz, Carlos, Black, James RM, Biswas, Dhruva, Campbell, Brittany B, Lee, Claudia, Colliver, Emma, Enfield, Katey SS, Hessey, Sonya, Hiley, Crispin T, Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J, Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad R, Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R, Rekhtman, Natasha, Travis, William D, Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G, McGranahan, Nicholas, Swanton, Charles, Jamal-Hanjani, Mariam, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Castignani, Carla, Bailey, Chris, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Peggs, Karl S, Selvaraju, Kayalvizhi, Thol, Kerstin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Prymas, Paulina, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
TRACERx Consortium
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. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

5. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

Abbosh, Christopher, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Le Quesne, John, Moore, David A., Veeriah, Selvaraju, Rosenthal, Rachel, Marafioti, Teresa, Kirkizlar, Eser, Watkins, Thomas B. K., McGranahan, Nicholas, Ward, Sophia, Martinson, Luke, Riley, Joan, Fraioli, Francesco, Al Bakir, Maise, Grnroos, Eva, Zambrana, Francisco, Endozo, Raymondo, Bi, Wenya Linda, Fennessy, Fiona M., Sponer, Nicole, Johnson, Diana, Laycock, Joanne, Shafi, Seema, Czyzewska-Khan, Justyna, Rowan, Andrew, Chambers, Tim, Matthews, Nik, Turajlic, Samra, Hiley, Crispin, Lee, Siow Ming, Forster, Martin D., Ahmad, Tanya, Falzon, Mary, Borg, Elaine, Lawrence, David, Hayward, Martin, Kolvekar, Shyam, Panagiotopoulos, Nikolaos, Janes, Sam M., Thakrar, Ricky, Ahmed, Asia, Blackhall, Fiona, Summers, Yvonne, Hafez, Dina, Naik, Ashwini, Ganguly, Apratim, Kareht, Stephanie, Shah, Rajesh, Joseph, Leena, Marie Quinn, Anne, Crosbie, Phil A., Naidu, Babu, Middleton, Gary, Langman, Gerald, Trotter, Simon, Nicolson, Marianne, Remmen, Hardy, Kerr, Keith, Chetty, Mahendran, Gomersall, Lesley, Fennell, Dean A., Nakas, Apostolos, Rathinam, Sridhar, Anand, Girija, Khan, Sajid, Russell, Peter, Ezhil, Veni, Ismail, Babikir, Irvin-Sellers, Melanie, Prakash, Vineet, Lester, Jason F., Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Oukrif, Dahmane, Akarca, Ayse U., Hartley, John A., Lowe, Helen L., Lock, Sara, Iles, Natasha, Bell, Harriet, Ngai, Yenting, Elgar, Greg, Szallasi, Zoltan, Schwarz, Roland F., Herrero, Javier, Stewart, Aengus, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Hackshaw, Allan, Shaw, Jacqui A., Zimmermann, Bernhard G., Swanton, Charles, Bosshard-Carter, Leticia, Goh, Gerald, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Horswell, Stuart, Bakir, Maise Al, Mitter, Richard, Escudero, Mickael, Xu, Hang, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Nye, Emma, Graca, Sofia, Joshi, Kroopa, Furness, Andrew, Ben Aissa, Assma, Wong, Yien Ning Sophia, Georgiou, Andy, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Taylor, Magali, Choudhary, Junaid, Califano, Raffaele, Taylor, Paul, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Moss, Stuart, Idries, Faiza, Bishop, Paul, Chaturvedi, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Rogan, Jane, Smith, Elaine, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Djearaman, Madava, Quesne, John Le, Thomas, Anne, Walter, Harriet, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Primrose, Lindsay, Amadi, Anita, Palmer, Shirley, Miller, Joy, Buchan, Keith, Edwards, Alison, Morgan, Fiona, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Dentro, Stefan, and Dessimoz, Christophe

Subjects
Lung cancer -- Genetic aspects -- Development and progression, DNA sequencing -- Methods, Phylogeny -- Observations, Cancer metastasis -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies., Author(s): Christopher Abbosh [1]; Nicolai J. Birkbak [1, 2]; Gareth A. Wilson [1, 2]; Mariam Jamal-Hanjani [1]; Tudor Constantin [3]; Raheleh Salari [3]; John Le Quesne [4]; David A. Moore [...]

Published
2017
Full Text
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6. Abstracts for the Tenth International Conference on Brain Tumour Research and Therapy: Stalheim Hotel, Voss, Norway, September 6–9, 1993

Author

Abrahamsen, Tore G., Wesenberg, Finn, Mørk, Sverre, Allen, Jeffrey, Hayes, Roberta, DaRosso, Robert, Nirenberg, Anita, Ali-Osman, Francis, Akande, Nike, Amberger, V., Seulberger, H., Paganetti, P. A., Schwab, M. E., Schwab, M. E., Arita N., Ohnishi T., Hiraga S., Yamamoto H., Taki T., Izumoto S., Higuchi M., Hayakawa T., Kusakabe M., Sakakura T., Baldwin, N. G., Rice, C. D., Merchant, R. E., Ashmore, Sally M., Darling, J. L., Bailey, C. C., Balmaceda C., Diez B., Villablanca J., Walker R., Finlay J., Bergenheim, A. Tommy, Hartman, Magdalena, Bergh, Jonas, Ridderheim, PerÅke, Henriksson, Roger, Berens, Michael E., Rief, Monique D., Giese, Alf, Zackrisson, Björn, Elfversson, Jörgen, Bernstein, Mark, Cabantog, Alberto, Glen, Jennifer, Mikulis, David, Bjerkvig, Rolf, Pedersen, Paal-Henning, Mathisen, Berit, Mahesparan, Rupavathana, Haugland, Hans Kristian, Bernstein, Mark, Laperriere, Normand, Thomason, Cindy, Leung, Phil, Bobola M. S., Berger M. S., Silber J. R., Bongcam-Rudloff, Erik, Wang, Jia-Lun, Nistér, Monica, Westermark, Bengt, Brem, Steven, Breslow, Gary, Ho, Jason, Gately, Stephen, Takano, Shingo, Ward, William, Brada, M., Laing, R., Warrington, J., Brem, Steven, Engelhard, Herbert, Takano, Shingo, Gately, Stephen, Brem, Steven, Landau, Barry, Kwaan, Hau, Verrusio, Elaine, Buckner, J. C., Cascino, T. L., Schomberg, P. S., O'Fallon, J. R., Dinapoli, R. P., Burch, P. A., Shaw, E. G., Broaddus, William C., Hager-Loudon, Kathryn, Merchant, Randall E., Loudon, William, Couldwell, William T., Jiang, Jack B., Burns, David, Couldwell, William T., Weiss, Martin H., Apuzzo, Michael L. J., Desbaillets I., Tada M., de Tribolet N., Van Meir, E., Davis, R. L., Onda, K., Prados, M. D., Dolan, M. Eileen, Fleig, Matthew J., Friedman, Henry S., Ekstrand, A. Jonas, Longo, Nicola, James, C. David, Chou, D., Wijnhoven, B., Bellinzona, M., Nakagawa, M., Feuerstein B. G., Basu H. S., Dolan M. E., Bergeron C., Pellarm M., Deen D. F., Marton L. J., Finlay, Jonathan, Fulton D. S., Urtasun R. C., Giese, Alf, Scheck, Adrienne C., Geddes, J., Vowles, G. M., Ashmore, S. M., Gillespie, G. Y., Goldman, C. K., Tucker, M. T., Lyon, E., Tsai, J. -C., Gobbel, G. T., Chan, P. H., Greenberg, Hairy S., Chandler, W. F., Ensminger, W. D., Junck, L., Sandler, H., Bromberg, J., McKeever, P., Gonzalez G. G., Sarkar A., Basu H., Feuerstein B. G., Deen D. F., Haugland, Kr., Tysnes, Ole-Bjørn, Hiraga, Shoju, Arita, Norio, Ohnishi, Takanori, Taki, Takuyu, Yamamoto, Hiroshi, Higuchi, Masahide, Hayakawa, Toru, Isern, Erik, Unsgaard, Geirmund, Marthinsen, Anne Beate Langeland, Strickert, Trond, Helseth, Eirik, Hochberg F., Cosgrove R., Valenzuela R., Pardo F., Zervas N., Jenkins, Robert B., Ritland, Steven R., Hailing, Kevin C., Thibodeau, Stephen N., Juillerat L., Darekar P., Janzer R. C., Hamou M. F., Kato, Tsutomu, Sawamura, Yutaka, Tada, Mitsuhiro, Sakuma, Shirou, Sudo, Masako, Abe, Hiroshi, Kallio M., Leppää J., Nikula T., Nikkinen P., Gylling H., Färkkilä M., Hiltunen J., Jääskeläinen J., Liewendahl K., Keles, G. Evren, Berger, Mitchel S., Deliganis, Anna, Kellie S. J., De Graaf S. S. N., Bloemhof H., Johnston I., Uges D. D. R., Besser M., Chaseling R. W., Ouvrier R. A., Kitchen, N. D., Hughes, S., Beaney, R., Thomas, D. G. T., Kim D. H., Maeda T., Mohapatra G., Park S., Waldman F. W., Gray J. W., Koala, D., Silber, J., Berger, M., Krauseneck P., Müller B., Strik H., Warmuth-Metz M., Kuratsu, Jun-ichi, Takeshima, Hideo, Ushio, Yukitaka, Kretschmar, C., Grodman, H., Linggood, R., Kyritsis, A. P., Bondy, M., Cunningham, J., Xiao, M., Levin, V., Leeds, N., Bruner, J., Yung, W. K. A., Saya, H., Lampson, L. A., Nichols, M. R., Lampson, M. A., Dunne, A. D., Li, Hong, Hamou, Marie-France, Jaufeerally, Rehana, Diserens, Annie-Claire, Van Meir, Erwin, de Tribolet, Nicolas, Levin, V. A., Maor, M., Sawaya, R., Leavens, M., Woo, S., Thall, P., Gleason, M. J., Liang, Bertrand C., Ross, D. A., Meltzer, P. S., Trent, J. M., Greenberg, H. S., Lillehei K. O., Kong Q., DeMasters B. K., Withrow S. J., Macdonald D. R., Cairncross J. G., Ludwin S., Lee D., Cascino T., Buckner J., Dropcho E., Fulton D., Stewart D., Schold C., Wainman N., Eisenhauer E., Kirby S., Fisher B. J., Magrassi, L., Butti, G., Pezzotta, S., Milanesi∘, G., Matsutani, Masao, Marienhagen, Kirsten, Laerum, Ole Didrik, Baldwin, N. G., Merzak, Abderrahim, Koocheckpour, Shahriar, Roxanis, Yannis, Pilktngton, Geoffrey J., Nagai, Masakatsu, Watanabe, Kunihiko, Narita, Jun-ichi, Hagiwara, Hideaki, Noble, Mark, Nomura, K., Oyama, H., Motoo, M., Shibui, S., Tokuue, K., Akine, Y., Ohnishi, T., Arita, N., Hiraga, S., Hayakawa, T., Nygaard, Svein J. Tjoflaat, Tysnes, Ole-Bjørn, Pardo, F. S., Hsu, D. W., Hedley-Whyte, E. T., Efird, J., Schmidt, E. V., Marienhagen, Paal-Henning Pedersenl Kirsten, Pilkington, Geoffrey J., Clarke, Tracey M., Yu, Hui Tian, Rogers, Joan P., Stern, Robert, Phuphanich, Surasak, Greenberg, Harvey, Murtagh, R., Viloria, Jesus, Ransohoff, Joseph, Martin, Kimberly, Hatva, V. Erika, Rao, Jasti S., Mohanam, S., Rempel, Sandra A., Schwechheimer, Karl, Davis, Richard L., Cavenee, Webster K., Rosenblum, Mark L., Reifenberger, Guido, Liu, Lu, Ichimura, Koichi, Schmidt, Esther E., Collins, V. Peter, Revesz T., Scaravilli F., Cockburn H., Thomas D. G. T., Rice, C. D., Biron, R. T., Merchant, R. E., McKerrow, James, Sloane, Bonnie, Mikkelsen, Tom, Roosen, Norbert, Coopersmith, Peter, Smith, Robert, Rooprai, Harcharan Kaur, Maidment, Steven, Rucklidge, Garry, Volovsek, Anton, Rutka J. T., Smith S. L., Matsuzawa K., Sankar, A. A., Darling, J. L., Williams, S. R., Fukuyama K., Marton L. J., Ikeda, Jun, Selker, R. G., Vertosick, F. T., Goldenberg, M. T., Bindal, R., Diez B., Taratuto A., Picco P., Monges J., Martinez M., Pacheco G., Gamboni M., Schultz M., Silber J. R., Mueller B. A., Ewers T. G., Berger M. S., Shiraishi, T., Tabuchi, K., Nakagawa, S., Kihara, S., Stewart, D. J., Eapen, L., Agboola, O., Popovic, P., Goel, R., Raaphorst, P., Wong, P. T. T., Shimokawa, S., Oh-uchida, M., Hori, K., Markert C., Pflughaupt K. -W., Tada M., Diserens A. -C., Jauferrally R., Desbaillets I., Hamou M. -F., de Tribolet N., Takeshima H., Mochizuki H., Clifford J. L., Nishi T., Levin V. A., Lotan R., Saya H., Terzis, A. J. A., Arnold, H., Laerum, O. D., Bjerkvig, R., Taratuto A. L., Sevlever G., Diaz D., Di Tella M., Cuccia V., Pomata H., Gallo G., Dietze, A., Knopp, U., Thomas, R., Brada, M., Carnochan, P., Flux, G., Kitchen, N., Thomas, D., Zalutsky, M., Bigner, D., Tofilon, Philip, Borchardt, Paul, Torp, Sverre H., Dalen, Are, Tohyama, Takashi, Kubo, Osami, Takakura, Kintomo, Lee, Virginia M. -Y., Trojanowski, John Q., Nygaard, Svein, Urtasun, R. C., Parliament, M. B., McEwan, A. J., Mannan, R. H., Weibe, L. I., Unsgårp, G., Sonnewald, U., Gribbestad, I., Isern, E., Petersen, S. B., Wang J., Delgado D. A., Warr, Tracy J., Sheer, Denise, Gorman, Pat, Yamaguchi, F., Westphal, M., Anker, L., Hamel, W., Lücke, M., Shepard, M., Kleihues, P., Herrmann, H. D., Yung, W. K. Alfred, Taylor, Scott, and Steck, Peter A.

Published
1993
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7. Fc effector function contributes to the activity of human anti-CTLA-4 antibodies

Author

Arce Vargas, Frederick, Furness, Andrew J.S., Litchfield, Kevin, Joshi, Kroopa, Rosenthal, Rachel, Ghorani, Ehsan, Solomon, Isabelle, Lesko, Marta H., Ruef, Nora, Roddie, Claire, Henry, Jake Y., Spain, Lavinia, Ben Aissa, Assma, Georgiou, Andrew, Wong, Yien Ning Sophia, Smith, Myles, Strauss, Dirk, Hayes, Andrew, Nicol, David, O'Brien, Tim, Mårtensson, Linda, Ljungars, Anne, Teige, Ingrid, Frendéus, Björn, Pule, Martin, Marafioti, Teresa, Gore, Martin, Larkin, James, Turajlic, Samra, Swanton, Charles, Peggs, Karl S., Quezada, Sergio A., Harrington, Kevin, Melcher, Alan, Wotherspoon, Andrew, Francis, Nicholas, Challacombe, Ben, Fernando, Archana, Hazell, Steve, Chandra, Ashish, Pickering, Lisa, Lynch, Joanna, Rudman, Sarah, Chowdhury, Simon, Harrison-Phipps, Karen, Varia, Mary, Horsfield, Catherine, Polson, Alexander, Stamp, Gordon, O'Donnell, Marie, Drake, William, Hill, Peter, Hrouda, David, Mayer, Eric, Olsburgh, Jonathan, Kooiman, Gordon, O'Connor, Kevin, Stewart, Grant, Aitchison, Michael, Tran, Maxine, Fotiadis, Nicos, Verma, Hema, Lopez, Jose, Lester, Jason, Morgan, Fiona, Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Fennell, Dean, Shaw, Jacqui, Le Quesne, John, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lock, Sara, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Novasio, Juliette, Joseph, Leena, Bishop, Paul, Chaturvedi, Anshuman, Marie Quinn, Anne, Doran, Helen, leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Brady, Ged, Rothwell, Dominic, Gulati, Sakshi, Chemie, Francesca, Tugwood, Jonathan, Pierce, Jackie, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, George, Robert, Patrini, Davide, Falzon, Mary, Borg, Elaine, Khiroya, Reena, Jamal-Hanjani, Mariam, Wilson, Gareth, Juul Birkbak, Nicolai, Watkins, Thomas, McGranahan, Nicholas, Abbosh, Christopher, Horswell, Stuart, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Rowan, Andrew, Hiley, Crispin, Goldman, Jacki, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Shaw, Penny, Veeriah, Raju, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Hynds, Robert, Werner Sunderland, Mariana, Reading, James, Novelli, Marco, Oukrif, Dahmane, Janes, Sam, Forster, Martin, Ahmad, Tanya, Ming Lee, Siow, van Loo, Peter, Herrero, Javier, Hartley, John, Kevin Stone, Richard, Denner, Tamara, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Ward, Sophie, Elgar, Greg, Al-Bakir, Maise, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Papadatos-Pastos, Dionysis, Scarci, Marco, Gorman, Pat, Lowe, Helen, Ensell, Leah, Moore, David, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Tavares Barbosa, Monica, Nicholson, Andrew, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Elena Cufari, Maria, Carlo Ronquillo, John, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Ezhil, Veni, Prakash, Vineet, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Russell, Peter, Light, Teresa, Horey, Tracey, Blyth, Kevin, Dick, Craig, and Kirk, Alan

Abstract

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches.

Published
2018

8. Fc-Optimized Anti-CD25 depletes tumor-infiltrating regulatory T Cells and synergizes with PD-1 Blockade to eradicate established tumors

Author

Arce Vargas, Frederick, Furness, Andrew J.S., Solomon, Isabelle, Joshi, Kroopa, Mekkaoui, Leila, Lesko, Marta H., Miranda Rota, Enrique, Dahan, Rony, Georgiou, Andrew, Sledzinska, Anna, Ben Aissa, Assma, Franz, Dafne, Werner Sunderland, Mariana, Wong, Yien Ning Sophia, Henry, Jake Y., O’Brien, Tim, Nicol, David, Challacombe, Ben, Beers, Stephen A., Turajlic, Samra, Gore, Martin, Larkin, James, Swanton, Charles, Chester, Kerry A., Pule, Martin, Ravetch, Jeffrey V., Marafioti, Teresa, Peggs, Karl S., Quezada, Sergio A., Spain, Lavinia, Wotherspoon, Andrew, Francis, Nicholas, Smith, Myles, Strauss, Dirk, Hayes, Andrew, Soultati, Aspasia, Stares, Mark, Lynch, Joanna, Fotiadis, Nicos, Fernando, Archana, Hazell, Steve, Chandra, Ashish, Pickering, Lisa, Rudman, Sarah, Chowdhury, Simon, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Shafi, Seema, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Bosshard-Carter, Leticia, Goh, Gerald, Rosenthal, Rachel, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Wilson, Gareth, Birkbak, Nicolai J., Watkins, Thomas B.K., McGranahan, Nicholas, Horswell, Stuart, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Van Loo, Peter, Rowan, Andrew, Xu, Hang, Hiley, Crispin, Abbosh, Christopher, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Matthews, Nik, Elgar, Greg, Ward, Sophia, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Graca, Sofia, Al Bakir, Maise, Hartley, John A., Lowe, Helen L., Herrero, Javier, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, Kolvekar, Shyam, Falzon, Mary, Borg, Elaine, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Oukrif, Dahmane, Janes, Sam M., Thakrar, Ricky, Forster, Martin, Ahmad, Tanya, Lee, Siow Ming, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Joseph, Leena, Bishop, Paul, Chaturved, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Fennell, Dean, Shaw, Jacqui A., Le Quesne, John, Moore, David, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Amadi, Anita, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lester, Jason, Edwards, Alison, Morgan, Fiona, Adams, Haydn, Davies, Helen, Kornaszewska, Malgorzata, Attanoos, Richard, Lock, Sara, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Iles, Natasha, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jorda, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Ezhil, Veni, Ismail, Babikir, Irvin-sellers, Melanie, Prakash, Vineet, Russell, Peter, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, and Asante-Siaw, Julius

Subjects
hemic and immune systems, chemical and pharmacologic phenomena, R1
Abstract

Summary\ud \ud 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

9. Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Author

McGranahan, Nicholas, primary, Rosenthal, Rachel, additional, Hiley, Crispin T., additional, Rowan, Andrew J., additional, Watkins, Thomas B.K., additional, Wilson, Gareth A., additional, Birkbak, Nicolai J., additional, Veeriah, Selvaraju, additional, Van Loo, Peter, additional, Herrero, Javier, additional, Swanton, Charles, additional, Jamal-Hanjani, Mariam, additional, Shafi, Seema, additional, Czyzewska-Khan, Justyna, additional, Johnson, Diana, additional, Laycock, Joanne, additional, Bosshard-Carter, Leticia, additional, Gorman, Pat, additional, Hynds, Robert E., additional, Wilson, Gareth, additional, McGranahan, Nicholas, additional, Horswell, Stuart, additional, Mitter, Richard, additional, Escudero, Mickael, additional, Stewart, Aengus, additional, Rowan, Andrew, additional, Xu, Hang, additional, Turajlic, Samra, additional, Hiley, Crispin, additional, Abbosh, Christopher, additional, Goldman, Jacki, additional, Stone, Richard Kevin, additional, Denner, Tamara, additional, Matthews, Nik, additional, Elgar, Greg, additional, Ward, Sophia, additional, Costa, Marta, additional, Begum, Sharmin, additional, Phillimore, Ben, additional, Chambers, Tim, additional, Nye, Emma, additional, Graca, Sofia, additional, Al Bakir, Maise, additional, Joshi, Kroopa, additional, Furness, Andrew, additional, Ben Aissa, Assma, additional, Wong, Yien Ning Sophia, additional, Georgiou, Andy, additional, Quezada, Sergio, additional, Hartley, John A., additional, Lowe, Helen L., additional, Lawrence, David, additional, Hayward, Martin, additional, Panagiotopoulos, Nikolaos, additional, Kolvekar, Shyam, additional, Falzon, Mary, additional, Borg, Elaine, additional, Marafioti, Teresa, additional, Simeon, Celia, additional, Hector, Gemma, additional, Smith, Amy, additional, Aranda, Marie, additional, Novelli, Marco, additional, Oukrif, Dahmane, additional, Janes, Sam M., additional, Thakrar, Ricky, additional, Forster, Martin, additional, Ahmad, Tanya, additional, Lee, Siow Ming, additional, Papadatos-Pastos, Dionysis, additional, Carnell, Dawn, additional, Mendes, Ruheena, additional, George, Jeremy, additional, Navani, Neal, additional, Ahmed, Asia, additional, Taylor, Magali, additional, Choudhary, Junaid, additional, Summers, Yvonne, additional, Califano, Raffaele, additional, Taylor, Paul, additional, Shah, Rajesh, additional, Krysiak, Piotr, additional, Rammohan, Kendadai, additional, Fontaine, Eustace, additional, Booton, Richard, additional, Evison, Matthew, additional, Crosbie, Phil, additional, Moss, Stuart, additional, Idries, Faiza, additional, Joseph, Leena, additional, Bishop, Paul, additional, Chaturved, Anshuman, additional, Quinn, Anne Marie, additional, Doran, Helen, additional, Leek, Angela, additional, Harrison, Phil, additional, Moore, Katrina, additional, Waddington, Rachael, additional, Novasio, Juliette, additional, Blackhall, Fiona, additional, Rogan, Jane, additional, Smith, Elaine, additional, Dive, Caroline, additional, Tugwood, Jonathan, additional, Brady, Ged, additional, Rothwell, Dominic G., additional, Chemi, Francesca, additional, Pierce, Jackie, additional, Gulati, Sakshi, additional, Naidu, Babu, additional, Langman, Gerald, additional, Trotter, Simon, additional, Bellamy, Mary, additional, Bancroft, Hollie, additional, Kerr, Amy, additional, Kadiri, Salma, additional, Webb, Joanne, additional, Middleton, Gary, additional, Djearaman, Madava, additional, Fennell, Dean, additional, Shaw, Jacqui A., additional, Le Quesne, John, additional, Moore, David, additional, Nakas, Apostolos, additional, Rathinam, Sridhar, additional, Monteiro, William, additional, Marshall, Hilary, additional, Nelson, Louise, additional, Bennett, Jonathan, additional, Riley, Joan, additional, Primrose, Lindsay, additional, Martinson, Luke, additional, Anand, Girija, additional, Khan, Sajid, additional, Amadi, Anita, additional, Nicolson, Marianne, additional, Kerr, Keith, additional, Palmer, Shirley, additional, Remmen, Hardy, additional, Miller, Joy, additional, Buchan, Keith, additional, Chetty, Mahendran, additional, Gomersall, Lesley, additional, Lester, Jason, additional, Edwards, Alison, additional, Morgan, Fiona, additional, Adams, Haydn, additional, Davies, Helen, additional, Kornaszewska, Malgorzata, additional, Attanoos, Richard, additional, Lock, Sara, additional, Verjee, Azmina, additional, MacKenzie, Mairead, additional, Wilcox, Maggie, additional, Bell, Harriet, additional, Hackshaw, Allan, additional, Ngai, Yenting, additional, Smith, Sean, additional, Gower, Nicole, additional, Ottensmeier, Christian, additional, Chee, Serena, additional, Johnson, Benjamin, additional, Alzetani, Aiman, additional, Shaw, Emily, additional, Lim, Eric, additional, De Sousa, Paulo, additional, Barbosa, Monica Tavares, additional, Bowman, Alex, additional, Jordan, Simon, additional, Rice, Alexandra, additional, Raubenheimer, Hilgardt, additional, Proli, Chiara, additional, Cufari, Maria Elena, additional, Ronquillo, John Carlo, additional, Kwayie, Angela, additional, Bhayani, Harshil, additional, Hamilton, Morag, additional, Bakar, Yusura, additional, Mensah, Natalie, additional, Ambrose, Lyn, additional, Devaraj, Anand, additional, Buderi, Silviu, additional, Finch, Jonathan, additional, Azcarate, Leire, additional, Chavan, Hema, additional, Green, Sophie, additional, Mashinga, Hillaria, additional, Nicholson, Andrew G., additional, Lau, Kelvin, additional, Sheaff, Michael, additional, Schmid, Peter, additional, Conibear, John, additional, Ezhil, Veni, additional, Ismail, Babikir, additional, Irvin-sellers, Melanie, additional, Prakash, Vineet, additional, Russell, Peter, additional, Light, Teresa, additional, Horey, Tracey, additional, Danson, Sarah, additional, Bury, Jonathan, additional, Edwards, John, additional, Hill, Jennifer, additional, Matthews, Sue, additional, Kitsanta, Yota, additional, Suvarna, Kim, additional, Fisher, Patricia, additional, Keerio, Allah Dino, additional, Shackcloth, Michael, additional, Gosney, John, additional, Postmus, Pieter, additional, Feeney, Sarah, additional, Asante-Siaw, Julius, additional, Aerts, Hugo J.W.L., additional, Dentro, Stefan, additional, and Dessimoz, Christophe, additional

Published
2017
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12. Herstory Writers Workshop.

Author

Gorman, Pat

Subjects
*WOMEN'S history, *HERSTORY, *AUTHORS, *AWARDS, *EDUCATIONAL anthropology, *SEMINARS
Abstract

This article focuses on herstory. Erika Duncan, novelist and essayist, had a featured interview column for the Long island Weekly section of The New York Times for 3 years. She co-founded the alternative literary Women's Salon in 1970 in New York City to bring serious critical attention to the works of women. She has received numerous grants and awards for her work training teachers to use writing to break through barriers of disability, economic disadvantage, and childhood pain. When Erika Duncan offered to help any woman who had ever dreamed of writing a book about her life to find a window of entry, women of all ages and backgrounds enrolled in her project. Once the first group of writers was launched, Herstory grew rapidly, with branches across Long Island, including programs in prisons and workshops in Spanish. Working across barriers of race, culture, economics, and education, each writer learned how to rekindle a lost self she had banished or left far behind as she brought that lost self to the page.

Published
2004
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14. Sráid na Cathrach (B.)

Author

Sráid Na Cathrach (B.), Briain, Pádraig Ó, Malone, Paddy, Keeffe, Bernard O', Lynch, Martin, Mahon, Kevin Mc, Sexton, James, Morrissey, Martin, Kenzie, Arthur Mc, Kenzie, Pat Mc, Connor, Thomas O', Flynn, Thomas, Woulfe, Joe, Rynne, Gerry, Malone, P., Corbett, Paddy, Sharkey, Eddie, Kenzie, Patrick Mc, Flynn, John, Reidy, Paddy, Keeffe, John O', Bholf, Seosamh De, Riain, Gearóid Ó, Maoláin, Pádraig Ó, Cóinnigh, Pádraigh Mac, Gorman, Pat O', Brien, Tom O', Mahon, Martin Mc, and Wolfe, Tom

Subjects
Irish Travellers (Nomadic people), History, Folk poetry, local legends, Legal status, laws, etc, Mermaids, Manners and customs, Fires, Saint Brigid's Day, Signs and symbols, Animals, Cemeteries, Occupations, Marriage, Weather, Folklore, Treasure troves, Basket making, Schools, Rope trade, Commerce, Leprechauns, Traditional medicine, Thrushes, Bread, May (Month), Roads, Famine, 1845-1852, Shipwrecks, Clothing and dress, Ringforts, Nail craft, Land use, Dissenters, Religious, Ireland, Proverbs
Abstract

A collection of folklore and local history stories from Sráid na Cathrach (B.) (school) (Milltown Malbay, Co. Clare), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher Pádraig Ó Briain., There is an old story told in this locality and it is believed by the old people to be true... -- Explanation of the Parish Name Kilfarboy / Briain, Pádraig Ó -- In the hill of Ballivaskin there are huge stone walls... / Malone, Paddy -- A story is told of a ship that was wrecked in the White Strand about a hundred years ago... / Keeffe, Bernard O' -- Saint Joseph's Well / Lynch, Martin -- Weather Signs / Mahon, Kevin Mc -- Graveyards / Sexton, James -- Old Trade / Morrissey, Martin -- Linen Industry / Malone, Paddy -- Flannel Industry in Sráid na Cathrach / Sexton, James -- Nail-Making in Sráid na Cathrach / Kenzie, Arthur Mc -- Firkin-Making in Sráid na Cathrach / Kenzie, Pat Mc -- Basket-Making / Mahon, Kevin Mc -- Old Fort / Connor, Thomas O' -- How Miltown Got Its Name / Connor, Thomas O' -- Páirc an Leasa - Sráid na Cathrach / Sexton, James -- Old Treasures / Malone, Paddy -- Old Treasure / Mahon, Kevin Mc -- Story / Flynn, Thomas -- Old Cures / Keeffe, Bernard O' -- Old Cure / Woulfe, Joe -- The "Craos Ghalar" as it is called is a disease of the throat the cure for which belongs to the seventh son in a family... / Kenzie, Pat Mc -- Old Cure / Morrissey, Martin -- There is a herb growing on the side of walls... / Rynne, Gerry -- Old Cure / Malone, P. -- Old Cure / Kenzie, Arthur Mc -- Cure for Calves / Corbett, Paddy -- Saint Brigid's Cross / Sharkey, Eddie -- Famine / Connor, Thomas O' -- Famine / Morrissey, Martin -- Famine / Kenzie, Patrick Mc -- Famine / Malone, Paddy -- Famine / Rynne, Gerry -- Famine / Keeffe, Bernard O' -- A Story / Mahon, Kevin Mc -- Landlords / Kenzie, Arthur Mc -- Landlords / Sharkey, Eddie -- Old Story / Keeffe, Bernard O' -- Old Story / Keeffe, Bernard O' -- Old Story / Keeffe, Bernard O' -- Marriages / Mahon, Kevin Mc -- Marriages / Connor, Thomas O' -- Marriages / Rynne, Gerry -- Marriages / Kenzie, Patrick Mc -- Bread / Malone, Paddy -- Bread / Sharkey, Eddie -- Bread / Kenzie, Arthur Mc -- Bread / Rynne, Gerry -- Herbs / Kenzie, Arthur Mc -- Herbs / Flynn, John -- The people long ago had no dyes to colour their woollens but what they used to do was to pick the bark off the rock and it would not put on any colour but brown... / Rynne, Gerry -- The buachallán, praiseach bhuidhe, the nettle, the thistle, the dock, the fern, and the feilistrium are herbs that are damaging to land because they cover a lot of ground... / Malone, Paddy -- Mo Chomharsanacht / Mahon, Kevin Mc -- Mo Chomharsanacht / Sharkey, Eddie -- May Eve Customs / Malone, Paddy -- May Eve Customs / Reidy, Paddy -- May Eve Customs / Rynne, Gerry -- May Eve / Mahon, Kevin Mc -- Shipwrecks / Keeffe, John O' -- Shipwrecks / Connor, Thomas O' -- Cill Stuifín / Malone, Paddy -- Cill Stuifín / Sharkey, Eddie -- Cill Stuifín / Woulfe, Joe -- Daoine Cáiliúla / Connor, Thomas O' -- Daoine Cáiliúla / Reidy, Paddy -- Daoine Cáiliúla / Kenzie, Arthur Mc -- Daoine Cáiliúla / Malone, Paddy -- Daoine Cáiliúla / Woulfe, Joe -- Place Names / Morrissey, Martin -- There is a hill a half a mile outside the town... / Rynne, Gerry -- It is said that Loch Láir got its name from a horse and foal, that were in Freigh, that used to come there every day... / Malone, Paddy -- Mermaids / Reidy, Paddy -- Mermaids / Rynne, Gerry -- "A Dhomhnaill Uí Chonaill, an dtuigeann tú Gaedhilge? / Bholf, Seosamh De -- Seanfhocail / Riain, Gearóid Ó -- Seanfhocail / Maoláin, Pádraig Ó -- Wild Animals / Connor, Thomas O' -- Wild Animals / Malone, Paddy -- Wild Animals / Kenzie, Arthur Mc -- Taking the Butter / Morrissey, Martin -- Seanfhocail / Cóinnigh, Pádraigh Mac -- Tramps / Malone, Paddy -- Old Story / Gorman, Pat O' -- Chair-Making / Woulfe, Joe -- Basket-Making -- Sugan-Making / Malone, Paddy -- Canada Cross / Woulfe, Joe -- Rinneen Ambush / Malone, Paddy -- Old Schools / Flynn, Thomas -- Old Schools / Brien, Tom O' -- Old Schools / Lynch, Martin -- Shops / Mahon, Martin Mc -- Shops / Wolfe, Tom -- How Isleacopple Got Its Name / Rynne, Gerry -- Story / Malone, Paddy -- May Eve - A True Story / Lynch, Martin -- Burning of Miltown / Morrissey, Martin -- Leprechauns / Rynne, Gerry -- Leprechauns / Malone, Paddy, Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.

Published
1937
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15. Your Brainwaves… Our Bargains!

Author

Turner-Marsh, Denise, Tomkins, Hayley, Jackson, Gillian, Giblin, Jodie, Yates, Kim, Angus, Sue, Garvin, Angela, Gorman, Pat, Henderson, Sharon, Cowle, Penny, Dole, Frances, and Pettit, Natalie

Published
2017

16. Your Brainwaves….

Author

Tempest, Jean, Turner, Sharon, McEwen, Heather, Gorman, Pat, Hill, Georgia, Gray, Dawn, Breen, Barbara, Rogers, Rita, Williams, Jean, O'Keeffe, B, and Cottle, T

Published
2017

17. Your Brainwaves… Our Bargains!

Author

Brown, K., Newton, Lynne, Johnston, Deborah, Martin, Anthony, Garvin, Angela, Malloy, Sharron, Smith, E., Baldwin, Paul, Gorman, Pat, Brunton, Colleen, Richardson, Pat, and Pullum, Liz

Published
2016

18. Your Brainwaves… Our Bargains!

Author

Giblin, Jodie, Clarkson, S, David, Jason, Baldwin, Paul, Gorman, Pat, McKellar, Debbie, Hartley, Jacki, Morrison, Steph, Cairns, Judith, Johnson, Ann, Rutherford, Frances, Primrose, Charlotte, and Betts, Brian

Published
2016

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