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201. Reliability of liquid biopsy analysis: an inter-laboratory comparison of circulating tumor DNA extraction and sequencing with different platforms

Author

Koessler, Thibaud, primary, Paradiso, Viola, additional, Piscuoglio, Salvatore, additional, Nienhold, Ronny, additional, Ho, Liza, additional, Christinat, Yann, additional, Terracciano, Luigi M., additional, Cathomas, Gieri, additional, Wicki, Andreas, additional, McKee, Thomas A., additional, and Nouspikel, Thierry, additional

Published
2020
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202. Infiltration by IL22-Producing T Cells Promotes Neutrophil Recruitment and Predicts Favorable Clinical Outcome in Human Colorectal Cancer

Author

Tosti, Nadia, primary, Cremonesi, Eleonora, additional, Governa, Valeria, additional, Basso, Camilla, additional, Kancherla, Venkatesh, additional, Coto-Llerena, Mairene, additional, Amicarella, Francesca, additional, Weixler, Benjamin, additional, Däster, Silvio, additional, Sconocchia, Giuseppe, additional, Majno, Pietro Edoardo, additional, Christoforidis, Dimitri, additional, Tornillo, Luigi, additional, Terracciano, Luigi, additional, Ng, Charlotte K.Y., additional, Piscuoglio, Salvatore, additional, von Flüe, Markus, additional, Spagnoli, Giulio, additional, Eppenberger-Castori, Serenella, additional, Iezzi, Giandomenica, additional, and Droeser, Raoul Andre, additional

Published
2020
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204. Identification of Somatic Mutations in Thirty-year-old Serum Cell-free DNA From Patients With Breast Cancer: A Feasibility Study

Author

Ritter, Mathilde, primary, Paradiso, Viola, additional, Widmer, Patrik, additional, Garofoli, Andrea, additional, Quagliata, Luca, additional, Eppenberger-Castori, Serenella, additional, Soysal, Savas D., additional, Muenst, Simone, additional, Ng, Charlotte K.Y., additional, Piscuoglio, Salvatore, additional, Weber, Walter, additional, and Weber, Walter P., additional

Published
2020
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205. A Pygopus 2-Histone Interaction Is Critical for Cancer Cell Dedifferentiation and Progression in Malignant Breast Cancer

Author

Saxena, Meera, primary, Kalathur, Ravi K.R., additional, Rubinstein, Natalia, additional, Vettiger, Andrea, additional, Sugiyama, Nami, additional, Neutzner, Melanie, additional, Coto-Llerena, Mairene, additional, Kancherla, Venkatesh, additional, Ercan, Caner, additional, Piscuoglio, Salvatore, additional, Fischer, Jonas, additional, Fagiani, Ernesta, additional, Cantù, Claudio, additional, Basler, Konrad, additional, and Christofori, Gerhard, additional

Published
2020
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206. Prevention of dsRNA‐induced interferon signaling by AGO1x is linked to breast cancer cell proliferation

Author

Ghosh, Souvik, primary, Guimaraes, Joao C, additional, Lanzafame, Manuela, additional, Schmidt, Alexander, additional, Syed, Afzal Pasha, additional, Dimitriades, Beatrice, additional, Börsch, Anastasiya, additional, Ghosh, Shreemoyee, additional, Mittal, Nitish, additional, Montavon, Thomas, additional, Correia, Ana Luisa, additional, Danner, Johannes, additional, Meister, Gunter, additional, Terracciano, Luigi M, additional, Pfeffer, Sébastien, additional, Piscuoglio, Salvatore, additional, and Zavolan, Mihaela, additional

Published
2020
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208. High Expression of FAP in Colorectal Cancer Is Associated With Angiogenesis and Immunoregulation Processes

Author

Coto-Llerena, Mairene, primary, Ercan, Caner, additional, Kancherla, Venkatesh, additional, Taha-Mehlitz, Stephanie, additional, Eppenberger-Castori, Serenella, additional, Soysal, Savas D., additional, Ng, Charlotte K. Y., additional, Bolli, Martin, additional, von Flüe, Markus, additional, Nicolas, Guillaume P., additional, Terracciano, Luigi M., additional, Fani, Melpomeni, additional, and Piscuoglio, Salvatore, additional

Published
2020
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209. Corrigendum to “HMGA1 expression in human hepatocellular carcinoma correlates with poor prognosis and promotes tumor growth and migration in in vitro models” [Neoplasia 18 (2016) 724–731]

Author

Andreozzi, Mariacarla, primary, Quintavalle, Cristina, additional, Benz, David, additional, Quagliata, Luca, additional, Matter, Matthias, additional, Calabrese, Diego, additional, Tosti, Nadia, additional, Ruiz, Christian, additional, Trapani, Francesca, additional, Tornillo, Luigi, additional, Fusco, Alfredo, additional, Heim, Markus H., additional, Ng, Charlotte K.Y., additional, Pallante, Pierlorenzo, additional, Terracciano, Luigi M., additional, and Piscuoglio, Salvatore, additional

Published
2020
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210. Abstract B18: Patient-derived xenograft and organoids models of prostate cancer

Author

Karkampouna, Sofia, primary, la Manna, Federico, additional, De Filippo, Maria R., additional, Kiener, Mirjam, additional, De Menna, Marta, additional, Zoni, Eugenio, additional, Grosjean, Joel, additional, Klima, Irena, additional, Garofoli, Andrea, additional, Bolis, Marco, additional, Theurillat, Jean-Philippe, additional, Genitsch, Vera, additional, Keller, David, additional, Tijmen, Booij, additional, Stirnimann, Christian U., additional, Sboner, Andrea, additional, Ng, Charlotte K.Y., additional, Piscuoglio, Salvatore, additional, Spahn, Martin, additional, Rubin, Mark A., additional, Thalmann, George N., additional, and Kruithof-de Julio, Marianna, additional

Published
2020
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211. GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers

Author

Bianco, Gaia, primary, Coto-Llerena, Mairene, additional, Gallon, John, additional, Taha-Mehlitz, Stephanie, additional, Kancherla, Venkatesh, additional, Konantz, Martina, additional, Srivatsa, Sumana, additional, Montazeri, Hesam, additional, Panebianco, Federica, additional, De Menna, Marta, additional, Paradiso, Viola, additional, Ercan, Caner, additional, Dahmani, Ahmed, additional, Montaudon, Elodie, additional, Beerenwinkel, Niko, additional, Kruithof-de Julio, Marianna, additional, Terracciano, Luigi M., additional, Lengerke, Claudia, additional, Bidard, François-Clément, additional, Jeselsohn, Rinath M., additional, Marangoni, Elisabetta, additional, Ng, Charlotte K. Y., additional, and Piscuoglio, Salvatore, additional

Published
2020
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212. The Genomic Landscape of Prostate Cancer Brain Metastases

Author

Rodriguez, Antonio, primary, Gallon, John, additional, Akhoundova, Dilara, additional, Maletti, Sina, additional, Ferguson, Alison, additional, Cyrta, Joanna, additional, Amstutz, Ursula, additional, Garofoli, Andrea, additional, Paradiso, Viola, additional, Tomlins, Scott A., additional, Hewer, Ekkehard, additional, Genitsch, Vera, additional, Fleischmann, Achim, additional, Rushing, Elisabeth J., additional, Grobholz, Rainer, additional, Fischer, Ingeborg, additional, Jochum, Wolfram, additional, Cathomas, Gieri, additional, Bubendorf, Lukas, additional, Moch, Holger, additional, Ng, Charlotte K.Y., additional, Sommer, Silke Gillessen, additional, Piscuoglio, Salvatore, additional, and Rubin, Mark A., additional

Published
2020
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213. PD59-07 PERSONALISED ORGANOID DRUG TREATMENT AND THERAPY RESISTANCE ON NOVEL EARLY ONSET METASTASIS XENOGRAFT MODEL

Author

Karkampouna, Sofia, primary, La Manna, Federico, additional, De Filippo, Maria Rosaria, additional, De Menna, Marta, additional, Zoni, Eugenio, additional, Grosjean, Joël, additional, Klima, Irena, additional, Garofoli, Andrea, additional, Genitsch, Vera, additional, Keller, David, additional, Booij, Tijmen H., additional, Stirnimann, Christian U., additional, Sboner, Andrea, additional, Ng, Charlotte K.Y., additional, Piscuoglio, Salvatore, additional, Spahn, Martin, additional, Rubin, Mark A., additional, Thalmann*, George N., additional, and Julio, Marianna Kruithof-de, additional

Published
2020
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214. Patient-derived xenografts and organoids model therapy response in prostate cancer

Author

Karkampouna, Sofia, primary, La Manna, Federico, additional, De Filippo, Maria R., additional, Kiener, Mirjam, additional, De Menna, Marta, additional, Zoni, Eugenio, additional, Grosjean, Joël, additional, Klima, Irena, additional, Garofoli, Andrea, additional, Bolis, Marco, additional, Theurillat, Jean-Philippe, additional, Genitsch, Vera, additional, Keller, David, additional, Booij, Tijmen H., additional, Stirnimann, Christian U., additional, Eng, Kenneth, additional, Sboner, Andrea, additional, Ng, Charlotte K. Y., additional, Piscuoglio, Salvatore, additional, PC, Gray, additional, Spahn, Martin, additional, Rubin, Mark A., additional, Thalmann, George N., additional, and Julio, Marianna Kruithof-de, additional

Published
2020
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215. Prognostic significance of SDF-1 in colorectal cancer depends on CD8+ T-cell density

Author

Lalos, Alexandros, primary, Tülek, Ali, additional, Tosti, Nadia, additional, Mechera, Robert, additional, Wilhelm, Alexander, additional, Soysal, Savas, additional, Daester, Silvio, additional, Kancherla, Venkatesh, additional, Weixler, Benjamin, additional, Spagnoli, Giulio C., additional, Eppenberger-Castori, Serenella, additional, Terracciano, Luigi, additional, Piscuoglio, Salvatore, additional, Flüe, Markus von, additional, Posabella, Alberto, additional, and Droeser, Raoul, additional

Published
2020
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216. Hormone receptor and HER2 assessment in breast carcinoma metastatic to bone: A comparison between FNA cell blocks and decalcified core needle biopsies

Author

Zeng, Jennifer, primary, Piscuoglio, Salvatore, additional, Aggarwal, Gitika, additional, Magda, Joanna, additional, Friedlander, Maria A., additional, Murray, Melissa, additional, Akram, Muzaffar, additional, Reis‐Filho, Jorge S., additional, Weigelt, Britta, additional, and Edelweiss, Marcia, additional

Published
2019
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217. LATS1 but not LATS2 represses autophagy by a kinase-independent scaffold function

Author

Tang, Fengyuan, primary, Gao, Ruize, additional, Jeevan-Raj, Beena, additional, Wyss, Christof B., additional, Kalathur, Ravi K. R., additional, Piscuoglio, Salvatore, additional, Ng, Charlotte K. Y., additional, Hindupur, Sravanth K., additional, Nuciforo, Sandro, additional, Dazert, Eva, additional, Bock, Thomas, additional, Song, Shuang, additional, Buechel, David, additional, Morini, Marco F., additional, Hergovich, Alexander, additional, Matthias, Patrick, additional, Lim, Dae-Sik, additional, Terracciano, Luigi M., additional, Heim, Markus H., additional, Hall, Michael N., additional, and Christofori, Gerhard, additional

Published
2019
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218. Preoperative plasma fatty acid metabolites inform risk of prostate cancer progression and may be used for personalized patient stratification

Author

Zoni, Eugenio, primary, Minoli, Martina, additional, Bovet, Cédric, additional, Wehrhan, Anne, additional, Piscuoglio, Salvatore, additional, Ng, Charlotte K. Y., additional, Gray, Peter C., additional, Spahn, Martin, additional, Thalmann, George N., additional, and Kruithof-de Julio, Marianna, additional

Published
2019
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219. Epigenetic priming in chronic liver disease impacts the transcriptional and genetic landscapes of hepatocellular carcinoma.

Author

Gallon, John, Coto‐Llerena, Mairene, Ercan, Caner, Bianco, Gaia, Paradiso, Viola, Nuciforo, Sandro, Taha‐Melitz, Stephanie, Meier, Marie‐Anne, Boldanova, Tujana, Pérez‐del‐Pulgar, Sofía, Rodríguez‐Tajes, Sergio, von Flüe, Markus, Soysal, Savas D., Kollmar, Otto, Llovet, Josep M., Villanueva, Augusto, Terracciano, Luigi M., Heim, Markus H., Ng, Charlotte K. Y., and Piscuoglio, Salvatore

Abstract

Hepatocellular carcinomas (HCCs) usually arise from chronic liver disease (CLD). Precancerous cells in chronically inflamed environments may be 'epigenetically primed', sensitising them to oncogenic transformation. We investigated whether epigenetic priming in CLD may affect HCC outcomes by influencing the genomic and transcriptomic landscapes of HCC. Analysis of DNA methylation arrays from 10 paired CLD‐HCC identified 339 shared dysregulated CpG sites and 18 shared differentially methylated regions compared with healthy livers. These regions were associated with dysregulated expression of genes with relevance in HCC, including ubiquitin D (UBD), cytochrome P450 family 2 subfamily C member 19 (CYP2C19) and O‐6‐methylguanine‐DNA methyltransferase (MGMT). Methylation changes were recapitulated in an independent cohort of nine paired CLD‐HCC. High CLD methylation score, defined using the 124 dysregulated CpGs in CLD and HCC in both cohorts, was associated with poor survival, increased somatic genetic alterations and TP53 mutations in two independent HCC cohorts. Oncogenic transcriptional and methylation dysregulation is evident in CLD and compounded in HCC. Epigenetic priming in CLD sculpts the transcriptional landscape of HCC and creates an environment favouring the acquisition of genetic alterations, suggesting that the extent of epigenetic priming in CLD could influence disease outcome. [ABSTRACT FROM AUTHOR]

Published
2022
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220. YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis.

Author

Gao, Ruize, Kalathur, Ravi K R, Coto‐Llerena, Mairene, Ercan, Caner, Buechel, David, Shuang, Song, Piscuoglio, Salvatore, Dill, Michael T, Camargo, Fernando D, Christofori, Gerhard, and Tang, Fengyuan

Abstract

Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In this study, a combination of shRNA‐mediated synthetic lethality screening and transcriptomic analysis revealed the transcription factors YAP/TAZ as key drivers of Sorafenib resistance in hepatocellular carcinoma (HCC) by repressing Sorafenib‐induced ferroptosis. Mechanistically, in a TEAD‐dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling HCC cells to overcome Sorafenib‐induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. Our study uncovers a critical role of YAP/TAZ in the repression of ferroptosis and thus in the establishment of Sorafenib resistance in HCC, highlighting YAP/TAZ‐based rewiring strategies as potential approaches to overcome HCC therapy resistance. SYNOPSIS: Resistance to therapy occurs in most liver cancer patients treated with Sorafenib, and patients succumb to the disease. A synthetic lethal screen identified a regulatory circuit, which prevents ferroptosis and promotes cancer cell survival, thus promoting resistance to Sorafenib. The transcription factors YAP and TAZ stabilize ATF4 by promoting its nuclear import to cooperatively induce expression of SLC7A11, a cystine importer critical for glutathione synthesis.Glutathione synthesis and homeostasis are required to repress ferroptosis and to maintain Sorafenib resistance in liver cancer cells.Inhibition of Glutathione synthesis re‐sensitizes Sorafenib‐resistant cancer cells to Sorafenib therapy, which then induces ferroptosis and represses tumor growth in murine liver cancer models.Pharmacological repression of the anti‐oxidant pathways regulated by YAP/TAZ and ATF4 could re‐sensitize therapy‐resistant liver cancers to Sorafenib treatment. [ABSTRACT FROM AUTHOR]

Published
2021
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221. PipeIT: A Singularity Container for Molecular Diagnostic Somatic Variant Calling on the Ion Torrent Next-Generation Sequencing Platform

Author

Garofoli, Andrea, Paradiso, Viola, Montazeri, Hesam, Jermann, Philip M, Roma, Guglielmo, Tornillo, Luigi, Terracciano, Luigi M, Piscuoglio, Salvatore, and Ng, Kiu Yan Charlotte

Subjects
610 Medicine & health
Abstract

The accurate identification of somatic mutations has become a pivotal component of tumor profiling and precision medicine. In molecular diagnostics laboratories, somatic mutation analyses on the Ion Torrent sequencing platform are typically performed on the Ion Reporter platform, which requires extensive manual review of the results and lacks optimized analysis workflows for custom targeted sequencing panels. Alternative solutions that involve custom bioinformatics pipelines involve the sequential execution of software tools with numerous parameters, leading to poor reproducibility and portability. We describe PipeIT, a stand-alone Singularity container of a somatic mutation calling and filtering pipeline for matched tumor-normal Ion Torrent sequencing data. PipeIT is able to identify pathogenic variants in BRAF, KRAS, PIK3CA, CTNNB1, TP53, and other cancer genes that the clinical-grade Oncomine workflow identified. In addition, PipeIT analysis of tumor-normal paired data generated on a custom targeted sequencing panel achieved 100% positive predictive value and 99% sensitivity compared with the 68% to 80% positive predictive value and 92% to 96% sensitivity using the default tumor-normal paired Ion Reporter workflow, substantially reducing the need for manual curation of the results. PipeIT can be rapidly deployed to and ensures reproducible results in any laboratory and can be executed with a single command with minimal input files from the users.

Published
2019
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222. Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens

Author

Srivatsa, Sumana, Montazeri, Hesam, Bianco, Gaia, Coto-Llerena, Mairene, Ng, Charlotte K.Y., Piscuoglio, Salvatore, and Beerenwinkel, Niko

Subjects
Perturbation screen, SL partner, AXIN1-URI1, SLIdR, Driver genes, Synthetic lethality (SL), Causal inference
Abstract

Despite the progress in precision oncology, development of cancer therapies is limited by the dearth of suitable drug targets1. Novel candidate drug targets can be identified based on the concept of synthetic lethality (SL), which refers to pairs of genes for which an aberration in either gene alone is non-lethal, but co-occurrence of the aberrations is lethal to the cell. We developed SLIdR (Synthetic Lethal Identification in R), a statistical framework for identifying SL pairs from large-scale perturbation screens. SLIdR successfully predicts SL pairs even with small sample sizes while minimizing the number of false positive targets. We applied SLIdR to Project DRIVE data2 and found both established and novel pan-cancer and cancer type-specific SL pairs. We identified and experimentally validated a novel SL interaction between AXIN1 and URI1 in hepatocellular carcinoma, thus corroborating the potential of SLIdR to identify new SL-based drug targets., bioRxiv

Published
2019
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223. Publisher correction : Homologous recombination DNA repair defects in PALB2-associated breast cancers

Author

Li, Anqi, Geyer, Felipe C., Blecua, Pedro, Lee, Ju Youn, Selenica, Pier, Brown, David N., Pareja, Fresia, Lee, Simon S.K., Kumar, Rahul, Rivera, Barbara, Bi, Rui, Piscuoglio, Salvatore, Wen, Hannah Y., Lozada, John R., Gularte-Mérida, Rodrigo, Cavallone, Luca, Aghmesheh, Morteza, Amor, David, Andrews, Leslie, Antill, Yoland, Balleine, Rosemary, Beesley, Jonathan, Blackburn, Anneke, Bogwitz, Michael, Brown, Melissa, Burgess, Matthew, Burke, Jo, Butow, Phyllis, Caldon, Liz, Campbell, Ian, Christian, Alice, Clarke, Christine, Cohen, Paul, Crook, Ashley, Cui, James, Cummings, Margaret, Dawson, Sarah Jane, De Fazio, Anna, Delatycki, Martin, Dobrovic, Alex, Dudding, Tracy, Duijf, Pascal, Edkins, Edward, Edwards, Stacey, Farshid, Gelareh, Fellows, Andrew, Field, Michael, Flanagan, James, Fong, Peter, Forbes, John, Forrest, Laura, Fox, Stephen, French, Juliet, Friedlander, Michael, Ortega, David Gallego, Gattas, Michael, Giles, Graham, Gill, Grantley, Gleeson, Margaret, Greening, Sian, Haan, Eric, Harris, Marion, Hayward, Nick, Hickie, Ian, Hopper, John, Hunt, Clare, James, Paul, Jenkins, Mark, Kefford, Rick, Kentwell, Maira, Kirk, Judy, Kollias, James, Lakhani, Sunil, Lindeman, Geoff, Lipton, Lara, Lobb, Lizz, Lok, Sheau, Macrea, Finlay, Mann, Graham, Marsh, Deb, McLachlan, Sue Anne, Meiser, Bettina, Milne, Roger, Nightingale, Sophie, O’Connell, Shona, Pachter, Nick, Patterson, Briony, Phillips, Kelly, Saleh, Mona, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Scott, Clare, Scott, Rodney, Sexton, Adrienne, Shelling, Andrew, Simpson, Peter, Spigelman, Allan, Spurdle, Mandy, Stone, Jennifer, Taylor, Jessica, Thorne, Heather, Trainer, Alison, Trench, Georgia, Tucker, Kathy, Visvader, Jane, Walker, Logan, Wallis, Mathew, Williams, Rachael, Winship, Ingrid, Wu, Kathy, Young, Mary Anne, Rezoug, Zoulikha, Nguyen-Dumont, Tu, Peterlongo, Paolo, Tondini, Carlo, Terkelsen, Thorkild, Rønlund, Karina, Boonen, Susanne E., Mannerma, Arto, Winqvist, Robert, Janatova, Marketa, Rajadurai, Pathmanathan, Xia, Bing, Norton, Larry, Robson, Mark E., Ng, Pei Sze, Looi, Lai Meng, Southey, Melissa C., Weigelt, Britta, Soo-Hwang, Teo, Tischkowitz, Marc, Foulkes, William D., Reis-Filho, Jorge S., Li, Anqi, Geyer, Felipe C., Blecua, Pedro, Lee, Ju Youn, Selenica, Pier, Brown, David N., Pareja, Fresia, Lee, Simon S.K., Kumar, Rahul, Rivera, Barbara, Bi, Rui, Piscuoglio, Salvatore, Wen, Hannah Y., Lozada, John R., Gularte-Mérida, Rodrigo, Cavallone, Luca, Aghmesheh, Morteza, Amor, David, Andrews, Leslie, Antill, Yoland, Balleine, Rosemary, Beesley, Jonathan, Blackburn, Anneke, Bogwitz, Michael, Brown, Melissa, Burgess, Matthew, Burke, Jo, Butow, Phyllis, Caldon, Liz, Campbell, Ian, Christian, Alice, Clarke, Christine, Cohen, Paul, Crook, Ashley, Cui, James, Cummings, Margaret, Dawson, Sarah Jane, De Fazio, Anna, Delatycki, Martin, Dobrovic, Alex, Dudding, Tracy, Duijf, Pascal, Edkins, Edward, Edwards, Stacey, Farshid, Gelareh, Fellows, Andrew, Field, Michael, Flanagan, James, Fong, Peter, Forbes, John, Forrest, Laura, Fox, Stephen, French, Juliet, Friedlander, Michael, Ortega, David Gallego, Gattas, Michael, Giles, Graham, Gill, Grantley, Gleeson, Margaret, Greening, Sian, Haan, Eric, Harris, Marion, Hayward, Nick, Hickie, Ian, Hopper, John, Hunt, Clare, James, Paul, Jenkins, Mark, Kefford, Rick, Kentwell, Maira, Kirk, Judy, Kollias, James, Lakhani, Sunil, Lindeman, Geoff, Lipton, Lara, Lobb, Lizz, Lok, Sheau, Macrea, Finlay, Mann, Graham, Marsh, Deb, McLachlan, Sue Anne, Meiser, Bettina, Milne, Roger, Nightingale, Sophie, O’Connell, Shona, Pachter, Nick, Patterson, Briony, Phillips, Kelly, Saleh, Mona, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Scott, Clare, Scott, Rodney, Sexton, Adrienne, Shelling, Andrew, Simpson, Peter, Spigelman, Allan, Spurdle, Mandy, Stone, Jennifer, Taylor, Jessica, Thorne, Heather, Trainer, Alison, Trench, Georgia, Tucker, Kathy, Visvader, Jane, Walker, Logan, Wallis, Mathew, Williams, Rachael, Winship, Ingrid, Wu, Kathy, Young, Mary Anne, Rezoug, Zoulikha, Nguyen-Dumont, Tu, Peterlongo, Paolo, Tondini, Carlo, Terkelsen, Thorkild, Rønlund, Karina, Boonen, Susanne E., Mannerma, Arto, Winqvist, Robert, Janatova, Marketa, Rajadurai, Pathmanathan, Xia, Bing, Norton, Larry, Robson, Mark E., Ng, Pei Sze, Looi, Lai Meng, Southey, Melissa C., Weigelt, Britta, Soo-Hwang, Teo, Tischkowitz, Marc, Foulkes, William D., and Reis-Filho, Jorge S.

Abstract

Original article published in "npj Breast Cancer, (2019), 5, 1, (23), 10.1038/s41523-019-0115-9" In the original version of this paper, the link to the data record in the Data Availability Statement was incorrectly listed as https:// doi.org/10.6084/m9.figshare.8138912.44. The link has been corrected to https://doi.org/10.6084/m9.figshare.8138912. This has been corrected in the HTML and PDF versions of this article.

Published
2019

224. Homologous recombination DNA repair defects in PALB2-associated breast cancers

Author

Li, Anqi, Geyer, Felipe, Blecua, Pedro, Lee, Ju Youn, Selenica, Pier, Brown, David, Pareja, Fresia, Lee, Simon, Kumar, Rahul, Rivera, Barbara, Bi, Rui, Piscuoglio, Salvatore, Wen, Hannah, Lozada, John, Gularte-Merida, Rodrigo, Cavallone, Luca, Rezoug, Zoulikha, Nguyen-Dumont, Tu, Peterlongo, Paolo, Tondini, Carlo, Terkelsen, Thorkild, Ronlund, Karina, Boonen, Susanne, Mannerma, Arto, Winqvist, Robert, Janatova, Marketa, Rajadurai, Pathmanathan, Xia, Bing, Norton, Larry, Robson, Mark, Ng, Pei-Sze, Looi, Lai-Meng, Southey, Melissa, Weigelt, Britta, Soo-Hwang, Teo, Tischkowitz, Marc, Foulkes, William, Reis-Filho, Jorge, Duijf, Pascal, Li, Anqi, Geyer, Felipe, Blecua, Pedro, Lee, Ju Youn, Selenica, Pier, Brown, David, Pareja, Fresia, Lee, Simon, Kumar, Rahul, Rivera, Barbara, Bi, Rui, Piscuoglio, Salvatore, Wen, Hannah, Lozada, John, Gularte-Merida, Rodrigo, Cavallone, Luca, Rezoug, Zoulikha, Nguyen-Dumont, Tu, Peterlongo, Paolo, Tondini, Carlo, Terkelsen, Thorkild, Ronlund, Karina, Boonen, Susanne, Mannerma, Arto, Winqvist, Robert, Janatova, Marketa, Rajadurai, Pathmanathan, Xia, Bing, Norton, Larry, Robson, Mark, Ng, Pei-Sze, Looi, Lai-Meng, Southey, Melissa, Weigelt, Britta, Soo-Hwang, Teo, Tischkowitz, Marc, Foulkes, William, Reis-Filho, Jorge, and Duijf, Pascal

Abstract

Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.

Published
2019

226. Author Correction: Genomic characterization of metastatic breast cancers

Author

Bertucci, François, Ng, Charlotte K. Y., Patsouris, Anne, Droin, Nathalie, Piscuoglio, Salvatore, Carbuccia, Nadine, and Soria, Jean Charles

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

An Amendment to this paper has been published and can be accessed via a link at the top of the paper., Author(s): François Bertucci [sup.1] , Charlotte K. Y. Ng [sup.2] [sup.3] [sup.24] , Anne Patsouris [sup.4] [sup.5] , Nathalie Droin [sup.6] [sup.7] [sup.8] , Salvatore Piscuoglio [sup.2] [sup.3] , Nadine [...]

Published
2019
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227. Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma.

Author

Dimitrakopoulos, Christos, Hindupur, Sravanth Kumar, Colombi, Marco, Liko, Dritan, Ng, Charlotte K. Y., Piscuoglio, Salvatore, Behr, Jonas, Moore, Ariane L., Singer, Jochen, Ruscheweyh, Hans-Joachim, Matter, Matthias S., Mossmann, Dirk, Terracciano, Luigi M., Hall, Michael N., and Beerenwinkel, Niko

Subjects
DRUG target, DATA integration, HEPATOCELLULAR carcinoma, LABORATORY mice, HISTONE acetylation
Abstract

Background: Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood. Results: Here, we explored the effect of defined genetic changes on the transcriptome, proteome and phosphoproteome in twelve tumors from an mTOR-driven hepatocellular carcinoma mouse model. Using Network-based Integration of multi-omiCS data (NetICS), we detected 74 'mediators' that relay via molecular interactions the effects of genetic and miRNA expression changes. The detected mediators account for the effects of oncogenic mTOR signaling on the transcriptome, proteome and phosphoproteome. We confirmed the dysregulation of the mediators YAP1, GRB2, SIRT1, HDAC4 and LIS1 in human HCC. Conclusions: This study suggests that targeting pathways such as YAP1 or GRB2 signaling and pathways regulating global histone acetylation could be beneficial in treating HCC with hyperactive mTOR signaling. [ABSTRACT FROM AUTHOR]

Published
2021
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228. Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas

Author

Geyer, Felipe C., Li, Anqi, Papanastasiou, Anastasios D., Smith, Alison, Selenica, Pier, Burke, Kathleen A., Edelweiss, Marcia, Wen, Huei-Chi, Piscuoglio, Salvatore, Schultheis, Anne M., Martelotto, Luciano G., Pareja, Fresia, Brandes, Alissa, Lozada, John, Macedo, Gabriel S., de Filippo, Maria R., Jungbluth, Achim A., Foschini, Maria Pia, Wen, Hannah Y., Brogi, Edi, Palazzo, Juan, Rubin, Brian P., Ng, Charlotte K.Y., Norton, Larry, Rakha, Emad A., Varga, Zsuzsanna, Ellis, Ian O., Chandarlapaty, Sarat, Weigelt, Britta, and Reis-Filho, Jorge S.

Subjects
epithelial-myoepithelial carcinoma, breast cancer, copy number variation, single nucleotide variant, RNA-sequencing, whole-exome sequencing
Abstract

Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, of which a subset will progress to invasive or metastatic cancer. We sought to define the genomic landscape of adenomyoepitheliomas. Massively parallel sequencing revealed highly recurrent somatic mutations in HRAS and PI3K-AKT pathway-related genes. Strikingly, HRAS mutations were restricted to estrogen receptor (ER)-negative tumors, all affected codon 61, and all but one co-occurred with PIK3CA or PIK3R1 mutations. To interrogate the functional significance of HRAS Q61 mutations in adenomyoepithelial differentiation, we expressed HRASQ61R alone or in combination with PIK3CAH1047R in non-transformed ER-negative breast epithelial cells. HRASQ61R induced characteristic phenotypes of adenomyoepitheliomas such as the expression of myoepithelial markers and loss of e-cadherin, hyperactivation of AKT signaling, and transformative properties that were arrested by combination therapy with AKT and MEK inhibitors. Our results indicate that breast adenomyoepitheliomas often manifest a unique transformation program featuring HRAS activation.

Published
2018

230. Systematic Identification of Novel Cancer Genes through Analysis of Deep shRNA Perturbation Screens

Author

Montazeri, Hesam, primary, Coto-Llerena, Mairene, additional, Bianco, Gaia, additional, Zangene, Ehsan, additional, Taha-Mehlitz, Stephanie, additional, Paradiso, Viola, additional, Srivatsa, Sumana, additional, de Weck, Antoine, additional, Roma, Guglielmo, additional, Lanzafame, Manuela, additional, Bolli, Martin, additional, Beerenwinkel, Niko, additional, von Flüe, Markus, additional, Terracciano, Luigi M., additional, Piscuoglio, Salvatore, additional, and Ng, Charlotte K. Y., additional

Published
2019
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232. PipeIT

Author

Garofoli, Andrea, primary, Paradiso, Viola, additional, Montazeri, Hesam, additional, Jermann, Philip M., additional, Roma, Guglielmo, additional, Tornillo, Luigi, additional, Terracciano, Luigi M., additional, Piscuoglio, Salvatore, additional, and Ng, Charlotte K.Y., additional

Published
2019
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235. Infiltration by myeloperoxidase-positive neutrophils is an independent prognostic factor in breast cancer

Author

Zeindler, Jasmin, primary, Angehrn, Fiorenzo, additional, Droeser, Raoul, additional, Däster, Silvio, additional, Piscuoglio, Salvatore, additional, Ng, Charlotte K. Y., additional, Kilic, Ergin, additional, Mechera, Robert, additional, Meili, Samuel, additional, Isaak, Andrej, additional, Weber, Walter P., additional, Muenst, Simone, additional, and Soysal, Savas Deniz, additional

Published
2019
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237. Abstract 4699: Enriching tumor purity using a unique flow-sorting approach to elucidate clonal evolution in matched samples of squamous cell carcinoma of the lung

Author

Krause, Arthur, primary, Filippo, Maria R. De, additional, Lorber, Thomas, additional, Dietsche, Tanja, additional, Perrina, Valeria, additional, Ruiz, Christian, additional, Barrett, Michael T., additional, Piscuoglio, Salvatore, additional, Ng, Charlotte K., additional, and Bubendorf, Lukas, additional

Published
2019
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238. Abstract 2821: Gut commensal bacteria modulate functions of tumor-associated neutrophils in human colorectal cancer

Author

Governa, Valeria, primary, Cremonesi, Eleonora, additional, Calabrese, Diego, additional, Mele, Valentina, additional, Trella, Emanuele, additional, Droeser, Raoul A., additional, Bolli, Martin, additional, Eppenberger-Castori, Serenella, additional, Piscuoglio, Salvatore, additional, Ng, Charlotte K. y., additional, Garzon, Jesus Francisco Glaus, additional, Borsig, Lubor, additional, Janssen, Klaus-Peter, additional, Terracciano, Luigi M., additional, Spagnoli, Giulio Cesare, additional, Christoforidis, Dimitri, additional, Majno-Hurst, Pietro Edoardo, additional, and Iezzi, Giandomenica, additional

Published
2019
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239. Abstract 4612: HOXA13 drives hepatocytes proliferation and liver tumorigenesis in mice

Author

Bianco, Gaia, primary, Montazeri, Hesam, additional, Quagliata, Luca, additional, O'Connor, Tracy, additional, Ehmer, Ursula, additional, Oellinger, Rupert, additional, Matter, Mathias, additional, Gerhard M., Christofori, additional, Ng, Charlotte K.Y., additional, Piscuoglio, Salvatore, additional, Heikenwaelder, Mathias, additional, and Terracciano, Luigi M., additional

Published
2019
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240. Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors

Author

Blumer, Tanja, primary, Fofana, Isabel, additional, Matter, Matthias S., additional, Wang, Xueya, additional, Montazeri, Hesam, additional, Calabrese, Diego, additional, Coto‐Llerena, Mairene, additional, Boldanova, Tujana, additional, Nuciforo, Sandro, additional, Kancherla, Venkatesh, additional, Tornillo, Luigi, additional, Piscuoglio, Salvatore, additional, Wieland, Stefan, additional, Terracciano, Luigi M., additional, Ng, Charlotte K.Y., additional, and Heim, Markus H., additional

Published
2019
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241. Genomic characterization of metastatic breast cancers

Author

Bertucci, François, primary, Ng, Charlotte K. Y., additional, Patsouris, Anne, additional, Droin, Nathalie, additional, Piscuoglio, Salvatore, additional, Carbuccia, Nadine, additional, Soria, Jean Charles, additional, Dien, Alicia Tran, additional, Adnani, Yahia, additional, Kamal, Maud, additional, Garnier, Séverine, additional, Meurice, Guillaume, additional, Jimenez, Marta, additional, Dogan, Semih, additional, Verret, Benjamin, additional, Chaffanet, Max, additional, Bachelot, Thomas, additional, Campone, Mario, additional, Lefeuvre, Claudia, additional, Bonnefoi, Herve, additional, Dalenc, Florence, additional, Jacquet, Alexandra, additional, De Filippo, Maria R., additional, Babbar, Naveen, additional, Birnbaum, Daniel, additional, Filleron, Thomas, additional, Le Tourneau, Christophe, additional, and André, Fabrice, additional

Published
2019
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242. Therapeutic Targeting of CD146/MCAM Reduces Bone Metastasis in Prostate Cancer

Author

Zoni, Eugenio, primary, Astrologo, Letizia, additional, Ng, Charlotte K.Y., additional, Piscuoglio, Salvatore, additional, Melsen, Janine, additional, Grosjean, Joël, additional, Klima, Irena, additional, Chen, Lanpeng, additional, Snaar-Jagalska, Ewa B., additional, Flanagan, Kenneth, additional, van der Pluijm, Gabri, additional, Kloen, Peter, additional, Cecchini, Marco G., additional, Kruithof-de Julio, Marianna, additional, and Thalmann, George N., additional

Published
2019
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243. AGO1x prevents dsRNA-induced interferon signaling to promote breast cancer cell proliferation

Author

Ghosh, Souvik, primary, Guimaraes, Joao C, additional, Lanzafame, Manuela, additional, Schmidt, Alexander, additional, Syed, Afzal Pasha, additional, Dimitriades, Beatrice, additional, Börsch, Anastasiya, additional, Ghosh, Shreemoyee, additional, Correia, Ana Luisa, additional, Danner, Johannes, additional, Meister, Gunter, additional, Terracciano, Luigi M., additional, Piscuoglio, Salvatore, additional, and Zavolan, Mihaela, additional

Published
2019
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245. Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma

Author

Lee, Ju Youn, primary, Schizas, Michail, additional, Geyer, Felipe C., additional, Selenica, Pier, additional, Piscuoglio, Salvatore, additional, Sakr, Rita A., additional, Ng, Charlotte K.Y., additional, Carniello, Jose V. Scarpa, additional, Towers, Russell, additional, Giri, Dilip D., additional, de Andrade, Victor P., additional, Papanastasiou, Anastasios D., additional, Viale, Agnes, additional, Harris, Reuben S., additional, Solit, David B., additional, Weigelt, Britta, additional, Reis-Filho, Jorge S., additional, and King, Tari A., additional

Published
2019
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246. The Genomic Landscape of Mucinous Breast Cancer

Author

Pareja, Fresia, primary, Lee, Ju Youn, additional, Brown, David N, additional, Piscuoglio, Salvatore, additional, Gularte-Mérida, Rodrigo, additional, Selenica, Pier, additional, Da Cruz Paula, Arnaud, additional, Arunachalam, Sasi, additional, Kumar, Rahul, additional, Geyer, Felipe C, additional, Silveira, Catarina, additional, da Silva, Edaise M, additional, Li, Anqi, additional, Marchiò, Caterina, additional, Ng, Charlotte K Y, additional, Mariani, Odette, additional, Fuhrmann, Laetitia, additional, Wen, Hannah Y, additional, Norton, Larry, additional, Vincent-Salomon, Anne, additional, Brogi, Edi, additional, Reis-Filho, Jorge S, additional, and Weigelt, Britta, additional

Published
2019
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247. Expression of RET is associated with Oestrogen receptor expression but lacks prognostic significance in breast cancer

Author

Mechera, Robert, primary, Soysal, Savas D., additional, Piscuoglio, Salvatore, additional, Ng, Charlotte K. Y., additional, Zeindler, Jasmin, additional, Mujagic, Edin, additional, Däster, Silvio, additional, Glauser, Philippe, additional, Hoffmann, Henry, additional, Kilic, Ergin, additional, Droeser, Raoul A., additional, Weber, Walter P., additional, and Muenst, Simone, additional

Published
2019
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248. Establishing standardized immune phenotyping of metastatic melanoma by digital pathology

Author

Sobottka, Bettina, Nowak, Marta, Frei, Anja Laura, Haberecker, Martina, Merki, Samuel, Levesque, Mitchell P., Dummer, Reinhard, Moch, Holger, Koelzer, Viktor Hendrik, Aebersold, Rudolf, Ak, Melike, Al-Quaddoomi, Faisal S., Albinus, Jonas, Alborelli, Ilaria, Andani, Sonali, Attinger, Per-Olof, Bacac, Marina, Baumhoer, Daniel, Beck-Schimmer, Beatrice, Beerenwinkel, Niko, Beisel, Christian, Bernasconi, Lara, Bertolini, Anne, Bodenmiller, Bernd, Bonilla, Ximena, Casanova, Ruben, Chevrier, Stéphane, Chicherova, Natalia, D'Costa, Maya, Danenberg, Esther, Davidson, Natalie, Drăganmoch, Monica-Andreea, Engler, Stefanie, Erkens, Martin, Eschbach, Katja, Esposito, Cinzia, Fedier, André, Ferreira, Pedro, Ficek, Joanna, Frey, Bruno, Goetze, Sandra, Grob, Linda, Gut, Gabriele, Günther, Detlef, Haberecker, Martina, Haeuptle, Pirmin, Heinzelmann-Schwarz, Viola, Herter, Sylvia, Holtackers, Rene, Huesser, Tamara, Irmisch, Anja, Jacob, Francis, Jacobs, Andrea, Jaeger, Tim M., Jahn, Katharina, James, Alva R., Jermann, Philip M., Kahles, André, Kahraman, Abdullah, Kuebler, Werner, Kuipers, Jack, Kunze, Christian P., Kurzeder, Christian, Lehmann, Kjong-Van, Lugert, Sebastian, Maass, Gerd, Manz, Markus G., Markolin, Philipp, Mena, Julien, Menzel, Ulrike, Metzler, Julian M., Miglino, Nicola, Milani, Emanuela S., Muenst, Simone, Murri, Riccardo, Ng, Charlotte K.Y., Nicolet, Stefan, Pedrioli, Patrick G.A., Pelkmans, Lucas, Piscuoglio, Salvatore, Prummer, Michael, Ritter, Mathilde, Rommel, Christian, Rosano-González, María L., Rätsch, Gunnar, Santacroce, Natascha, del Castillo, Jacobo Sarabia, Schlenker, Ramona, Schwalie, Petra C., Schwan, Severin, Schär, Tobias, Senti, Gabriela, Singer, Franziska, Sivapatham, Sujana, Snijder, Berend, Sreedharan, Vipin T., Stark, Stefan, Stekhoven, Daniel J., Theocharides, Alexandre P.A., Thomas, Tinu M., Tolnay, Markus, Tosevski, Vinko, Toussaint, Nora C., Tuncel, Mustafa A., Tusup, Marina, Van Drogen, Audrey, Vetter, Marcus, Vlajnic, Tatjana, Weber, Sandra, Weber, Walter P., Wegmann, Rebekka, Weller, Michael, Wendt, Fabian, Wey, Norbert, Wicki, Andreas, Wildschut, Mattheus HE, Wollscheid, Bernd, Yu, Shuqing, Ziegler, Johanna, Zimmermann, Marc, Zoche, Martin, and Zuend, Gregor

Abstract

CD8+ tumor-infiltrating T cells can be regarded as one of the most relevant predictive biomarkers in immune-oncology. Highly infiltrated tumors, referred to as inflamed (clinically “hot”), show the most favorable response to immune checkpoint inhibitors in contrast to tumors with a scarce immune infiltrate called immune desert or excluded (clinically “cold”). Nevertheless, quantitative and reproducible methods examining their prevalence within tumors are lacking. We therefore established a computational diagnostic algorithm to quantitatively measure spatial densities of tumor-infiltrating CD8+ T cells by digital pathology within the three known tumor compartments as recommended by the International Immuno-Oncology Biomarker Working Group in 116 prospective metastatic melanomas of the Swiss Tumor Profiler cohort. Workflow robustness was confirmed in 33 samples of an independent retrospective validation cohort. The introduction of the intratumoral tumor center compartment proved to be most relevant for establishing an immune diagnosis in metastatic disease, independent of metastatic site. Cut-off values for reproducible classification were defined and successfully assigned densities into the respective immune diagnostic category in the validation cohort with high sensitivity, specificity, and precision. We provide a robust diagnostic algorithm based on intratumoral and stromal CD8+ T-cell densities in the tumor center compartment that translates spatial densities of tumor-infiltrating CD8+ T cells into the clinically relevant immune diagnostic categories “inflamed”, “excluded”, and “desert”. The consideration of the intratumoral tumor center compartment allows immune phenotyping in the clinically highly relevant setting of metastatic lesions, even if the invasive margin compartment is not captured in biopsy material.

Published
2021
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249. Utility of Serial cfDNA NGS for Prospective Genomic Analysis of Patients on a Phase I Basket Study.

Author

Smyth, Lillian M., Reichel, Jonathan B., Tang, Jiabin, Patel, Juber Ahamad A., Meng, Fanli, Selcuklu, Duygu S., Houck-Loomis, Brian, You, Daoqi, Samoila, Aliaksandra, Schiavon, Gaia, Li, Bob T., Razavi, Pedram, Piscuoglio, Salvatore, Reis-Filho, Jorge S., Taylor, Barry S., Baselga, José, Solit, David B., Hyman, David M., Berger, Michael F., and Chandarlapaty, Sarat

Subjects
CELL-free DNA, GENOMICS, GENETIC mutation, POLYMERASE chain reaction, SOMATIC mutation
Abstract

PURPOSE: Cell-free DNA (cfDNA) analysis offers a noninvasive means to access the tumor genome. Despite limited sensitivity of broad-panel sequencing for detecting low-frequency mutations in cfDNA, it may enable more comprehensive genomic characterization in patients with sufficiently high disease burden. We investigated the utility of large-panel cfDNA sequencing in patients enrolled to a Phase I AKT1 -mutant solid tumor basket study. METHODS: Patients had AKT1 E17K-mutant solid tumors and were treated on the multicenter basket study (ClinicalTrials.gov identifier: NCT01226316) of capivasertib, an AKT inhibitor. Serial plasma samples were prospectively collected and sequenced using exon-capture next-generation sequencing (NGS) analysis of 410 genes (Memorial Sloan Kettering [MSK]-Integrated Molecular Profiling of Actionable Cancer Target [IMPACT]) and allele-specific droplet digital polymerase chain reaction (ddPCR) for AKT1 E17K. Tumor DNA (tDNA) NGS (MSK-IMPACT) was also performed on available pretreatment tissue biopsy specimens. RESULTS: Among 25 patients, pretreatment plasma samples were sequenced to an average coverage of 504×. Somatic mutations were called in 20/25 (80%), with mutant allele fractions highly concordant with ddPCR of AKT1 E17K (r 2 = 0.976). Among 17 of 20 cfDNA-positive patients with available tDNA for comparison, mutational concordance was acceptable, with 82% of recurrent mutations shared between tissue and plasma. cfDNA NGS captured additional tumor heterogeneity, identifying mutations not observed in tDNA in 38% of patients, and revealed oncogenic mutations in patients without available baseline tDNA. Longitudinal cfDNA NGS (n = 98 samples) revealed distinct patterns of clonal dynamics in response to therapy. CONCLUSION: Large gene panel cfDNA NGS is feasible for patients with high disease burden and is concordant with single-analyte approaches, providing a robust alternative to ddPCR with greater breadth. cfDNA NGS can identify heterogeneity and potentially biologically informative and clinically relevant alterations. [ABSTRACT FROM AUTHOR]

Published
2021
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250. Mutation profiling of key cancer genes in primary breast cancers and their distant metastases

Author

Schrijver, Willemijne A.M.E., Selenica, Pier, Lee, Ju Youn, Ng, Charlotte K.Y., Burke, Kathleen A., Piscuoglio, Salvatore, Berman, Samuel H., Reis-Filho, Jorge S., Weigelt, Britta, Van Diest, Paul J., Moelans, Cathy B., Schrijver, Willemijne A.M.E., Selenica, Pier, Lee, Ju Youn, Ng, Charlotte K.Y., Burke, Kathleen A., Piscuoglio, Salvatore, Berman, Samuel H., Reis-Filho, Jorge S., Weigelt, Britta, Van Diest, Paul J., and Moelans, Cathy B.

Published
2018

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