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8 results on '"Rehan Akbani"'

1. Tumor-intrinsic SIRPA promotes sensitivity to checkpoint inhibition immunotherapy in melanoma

Author

Zhicheng Zhou, Mei-Ju May Chen, Yikai Luo, Kamalika Mojumdar, Xin Peng, Hu Chen, Shweta V. Kumar, Rehan Akbani, Yiling Lu, and Han Liang

Subjects
Proteomics, Cancer Research, Mice, Oncology, Animals, Humans, Immunotherapy, CD8-Positive T-Lymphocytes, Melanoma, B7-H1 Antigen, Ecosystem
Abstract

Checkpoint inhibition immunotherapy has revolutionized cancer treatment, but many patients show resistance. Here we perform integrative transcriptomic and proteomic analyses on emerging immuno-oncology targets across multiple clinical cohorts of melanoma under anti-PD-1 treatment, on both bulk and single-cell levels. We reveal a surprising role of tumor-intrinsic SIRPA in enhancing antitumor immunity, in contrast to its well-established role as a major inhibitory immune modulator in macrophages. The loss of SIRPA expression is a marker of melanoma dedifferentiation, a key phenotype linked to immunotherapy efficacy. Inhibition of SIRPA in melanoma cells abrogates tumor killing by activated CD8

Published
2021

2. Large-Scale Characterization of Drug Responses of Clinically Relevant Proteins in Cancer Cell Lines

Author

Han Liang, Shwetha V. Kumar, Nupur T. Pande, Rehan Akbani, Gordon B. Mills, Andre Schultz, Joe W. Gray, Nicole K. Nesser, Yiling Lu, Ioannis K. Zervantonakis, Erika von Euw, Dennis J. Slamon, Mei-Ju May Chen, Paul T. Spellman, Yikai Luo, Meenhard Herlyn, Joan S. Brugge, Christopher Boniface, Katie Johnson-Camacho, Anil Korkut, Wei Zhao, Zhenlin Ju, Michael A. Davies, Taru A. Muranen, Jun Li, and Yancey Lawrence

Subjects
Proteomics, 0301 basic medicine, Drug, Cancer Research, Cell Survival, Computer science, media_common.quotation_subject, Protein Array Analysis, Antineoplastic Agents, Drug resistance, Computational biology, Article, User-Computer Interface, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Neoplasms, Drug response, Humans, Molecular Targeted Therapy, Protein Interaction Maps, Cell Proliferation, media_common, Disease mechanisms, Computational Biology, Cell Biology, Data portal, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer cell, Protein microarray, Cancer cell lines
Abstract

Perturbation biology is a powerful approach to modeling quantitative cellular behaviors and understanding detailed disease mechanisms. However, large-scale protein response resources of cancer cell lines to perturbations are not available, resulting in a critical knowledge gap. Here we generated and compiled perturbed expression profiles of ~210 clinically relevant proteins in >12,000 cancer cell line samples in response to ~170 drug compounds using reverse-phase protein arrays. We show that integrating perturbed protein response signals provides mechanistic insights into drug resistance, increases the predictive power for drug sensitivity, and helps identify effective drug combinations. We build a systematic map of “protein-drug” connectivity and develop a user-friendly data portal for community use. Our study provides a rich resource to investigate the behaviors of cancer cells and the dependencies of treatment responses, thereby enabling a broad range of biomedical applications.

Published
2020

3. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

Author

Siyuan Zheng, Andrew D. Cherniack, Ninad Dewal, Richard A. Moffitt, Ludmila Danilova, Bradley A. Murray, Antonio M. Lerario, Tobias Else, Theo A. Knijnenburg, Giovanni Ciriello, Seungchan Kim, Guillaume Assie, Olena Morozova, Rehan Akbani, Juliann Shih, Katherine A. Hoadley, Toni K. Choueiri, Jens Waldmann, Ozgur Mete, A. Gordon Robertson, Hsin-Ta Wu, Benjamin J. Raphael, Lina Shao, Matthew Meyerson, Michael J. Demeure, Felix Beuschlein, Anthony J. Gill, Stan B. Sidhu, Madson Q. Almeida, Maria C.B.V. Fragoso, Leslie M. Cope, Electron Kebebew, Mouhammed A. Habra, Timothy G. Whitsett, Kimberly J. Bussey, William E. Rainey, Sylvia L. Asa, Jérôme Bertherat, Martin Fassnacht, David A. Wheeler, Gary D. Hammer, Thomas J. Giordano, Roel G.W. Verhaak, Guillaume Assié, Hsin-Tu Wu, Madson Almeida, Maria Candida Barisson Fragoso, Mouhammed Amir Habra, Christopher Benz, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Yaron S.N. Butterfield, Rebecca Carlsen, Noreen Dhalla, Ranabir Guin, Robert A. Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Haiyan I. Li, Lynette Lim, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Peter J. Park, Matthias Kroiss, Jianjiong Gao, Chris Sander, Nikolaus Schultz, Corbin D. Jones, Raju Kucherlapati, Piotr A. Mieczkowski, Joel S. Parker, Charles M. Perou, Donghui Tan, Umadevi Veluvolu, Matthew D. Wilkerson, D. Neil Hayes, Marc Ladanyi, Marcus Quinkler, J. Todd Auman, Ana Claudia Latronico, Berenice B. Mendonca, Mathilde Sibony, Zack Sanborn, Michelle Bellair, Christian Buhay, Kyle Covington, Mahmoud Dahdouli, Huyen Dinh, Harsha Doddapaneni, Brittany Downs, Jennifer Drummond, Richard Gibbs, Walker Hale, Yi Han, Alicia Hawes, Jianhong Hu, Nipun Kakkar, Divya Kalra, Ziad Khan, Christine Kovar, Sandy Lee, Lora Lewis, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Liu Xi, Bertrand Dousset, Lionel Groussin, Rossella Libé, Lynda Chin, Sheila Reynolds, Ilya Shmulevich, Sudha Chudamani, Jia Liu, Laxmi Lolla, Ye Wu, Jen Jen Yeh, Saianand Balu, Tom Bodenheimer, Alan P. Hoyle, Stuart R. Jefferys, Shaowu Meng, Lisle E. Mose, Yan Shi, Janae V. Simons, Matthew G. Soloway, Junyuan Wu, Wei Zhang, Kenna R. Mills Shaw, John A. Demchok, Ina Felau, Margi Sheth, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Tanja Davidsen, Catherine Crawford, Carolyn M. Hutter, Heidi J. Sofia, Jeffrey Roach, Wiam Bshara, Carmelo Gaudioso, Carl Morrison, Patsy Soon, Shelley Alonso, Julien Baboud, Todd Pihl, Rohini Raman, Qiang Sun, Yunhu Wan, Rashi Naresh, Harindra Arachchi, Rameen Beroukhim, Scott L. Carter, Juok Cho, Scott Frazer, Stacey B. Gabriel, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Michael S. Noble, Gordon Saksena, Steven E. Schumacher, Carrie Sougnez, Doug Voet, Hailei Zhang, Jay Bowen, Sara Coppens, Julie M. Gastier-Foster, Mark Gerken, Carmen Helsel, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Stephen Baylin, James G. Herman, Janine LoBello, Aprill Watanabe, David Haussler, Amie Radenbaugh, Arjun Rao, Jingchun Zhu, Detlef K. Bartsch, Silviu Sbiera, Bruno Allolio, Timo Deutschbein, Cristina Ronchi, Victoria M. Raymond, Michelle Vinco, Linda Amble, Moiz S. Bootwalla, Phillip H. Lai, David J. Van Den Berg, Daniel J. Weisenberger, Bruce Robinson, Zhenlin Ju, Hoon Kim, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kanishka Sircar, Qianghu Wang, Kosuke Yoshihara, Peter W. Laird, Yu Fan, Wenyi Wang, Eve Shinbrot, Martin Reincke, John N. Weinstein, Sam Meier, and Timothy Defreitas

Subjects
Adult, Male, 0301 basic medicine, Cancer Research, Adolescent, Genomics, Biology, Genome, TERF2, Article, Disease-Free Survival, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Outcome Assessment, Health Care, Adrenocortical Carcinoma, medicine, Humans, Adrenocortical carcinoma, Genetic Predisposition to Disease, Child, Aged, Aged, 80 and over, Genetics, Genome, Human, business.industry, Gene Expression Profiling, Cell Biology, DNA Methylation, Middle Aged, Prognosis, medicine.disease, Adrenal Cortex Neoplasms, Human genetics, 3. Good health, Gene Expression Regulation, Neoplastic, Gene expression profiling, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Mutation, Cancer cell, DNA methylation, Cancer research, Female, Human genome, business
Abstract

We describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.

Published
2016

4. Integrated Molecular Characterization of Uterine Carcinosarcoma

Author

Andrew D. Cherniack, Hui Shen, Vonn Walter, Chip Stewart, Bradley A. Murray, Reanne Bowlby, Xin Hu, Shiyun Ling, Robert A. Soslow, Russell R. Broaddus, Rosemary E. Zuna, Gordon Robertson, Peter W. Laird, Raju Kucherlapati, Gordon B. Mills, John N. Weinstein, Jiashan Zhang, Rehan Akbani, Douglas A. Levine, Adrian Ally, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Stephen B. Baylin, Rameen Beroukhim, Tom Bodenheimer, Faina Bogomolniy, Lori Boice, Moiz S. Bootwalla, Jay Bowen, Russell Broaddus, Denise Brooks, Rebecca Carlsen, Juok Cho, Eric Chuah, Sudha Chudamani, Kristian Cibulskis, Melissa Cline, Fanny Dao, Mutch David, John A. Demchok, Noreen Dhalla, Sean Dowdy, Ina Felau, Martin L. Ferguson, Scott Frazer, Jessica Frick, Stacey Gabriel, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, Manaswi Gupta, David Haussler, D. Neil Hayes, David I. Heiman, Julian Hess, Katherine A. Hoadley, Robert Hoffmann, Robert A. Holt, Alan P. Hoyle, Mei Huang, Carolyn M. Hutter, Stuart R. Jefferys, Steven J.M. Jones, Corbin D. Jones, Rupa S. Kanchi, Cyriac Kandoth, Katayoon Kasaian, Sarah Kerr, Jaegil Kim, Phillip H. Lai, Eric Lander, Michael S. Lawrence, Darlene Lee, Kristen M. Leraas, Ignaty Leshchiner, Tara M. Lichtenberg, Pei Lin, Jia Liu, Wenbin Liu, Yuexin Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Dennis T. Maglinte, Marco A. Marra, Michael Mayo, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Richard A. Moore, Lisle E. Mose, Andrew J. Mungall, Karen Mungall, Rashi Naresh, Michael S. Noble, Narciso Olvera, Joel S. Parker, Charles M. Perou, Amy H. Perou, Todd Pihl, Amie J. Radenbaugh, Nilsa C. Ramirez, W. Kimryn Rathmell, Jeffrey Roach, A. Gordon Robertson, Sara Sadeghi, Gordon Saksena, Helga B. Salvesen, Jacqueline E. Schein, Steven E. Schumacher, Margi Sheth, Yan Shi, Juliann Shih, Janae V. Simons, Payal Sipahimalani, Tara Skelly, Heidi J. Sofia, Matthew G. Soloway, Carrie Sougnez, Charlie Sun, Angela Tam, Donghui Tan, Roy Tarnuzzer, Nina Thiessen, Leigh B. Thorne, Kane Tse, Jill Tseng, David J. Van Den Berg, Umadevi Veluvolu, Roel G.W. Verhaak, Doug Voet, Amanda von Bismarck, Yunhu Wan, Zhining Wang, Chen Wang, Daniel J. Weisenberger, Matthew D. Wilkerson, Boris Winterhoff, Lisa Wise, Tina Wong, Ye Wu, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Hailei Zhang, Wei Zhang, Jing-chun Zhu, and Erik Zmuda

Subjects
0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, DNA Copy Number Variations, medicine.disease_cause, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Carcinosarcoma, medicine, PTEN, Humans, Epigenetics, Uterine Neoplasm, Epigenomics, biology, Gene signature, medicine.disease, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Mutation, Uterine Neoplasms, Cancer research, biology.protein, Female, KRAS
Abstract

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

Published
2016

5. Characterization of Human Cancer Cell Lines by Reverse-phase Protein Arrays

Author

John V. Heymach, Qinghua Yu, Rehan Akbani, Gordon B. Mills, Jeffrey N. Myers, Wanleng Deng, Guo Chen, Yiling Lu, Jun Li, Han Liang, Shiyun Ling, Dennis J. Slamon, Dylan Conklin, A. Karina Eterovic, John D. Minna, Erika von Euw, Wenbin Liu, Zhenlin Ju, Christopher P. Vellano, Paul Roebuck, Lauren Averett Byers, Wei Zhao, Y.N. Vashisht Gopal, Adi F. Gazdar, and Michael A. Davies

Subjects
0301 basic medicine, Proteomics, Cancer Research, Epithelial-Mesenchymal Transition, Protein Array Analysis, Biology, medicine.disease_cause, Article, Transcriptome, 03 medical and health sciences, Cell Line, Tumor, medicine, Humans, RNA, Messenger, Nuclear protein, Transcription factor, Mutation, Reverse phase protein lysate microarray, RNA, Computational Biology, Nuclear Proteins, Cell Biology, Cell biology, Neoplasm Proteins, DNA-Binding Proteins, ErbB Receptors, 030104 developmental biology, Oncology, Signal transduction, Transcription Factors
Abstract

Cancer cell lines are major model systems for mechanistic investigation and drug development. However, protein expression data linked to high-quality DNA, RNA, and drug-screening data have not been available across a large number of cancer cell lines. Using reverse-phase protein arrays, we measured expression levels of ∼230 key cancer-related proteins in >650 independent cell lines, many of which have publically available genomic, transcriptomic, and drug-screening data. Our dataset recapitulates the effects of mutated pathways on protein expression observed in patient samples, and demonstrates that proteins and particularly phosphoproteins provide information for predicting drug sensitivity that is not available from the corresponding mRNAs. We also developed a user-friendly bioinformatic resource, MCLP, to help serve the biomedical research community.

Published
2016

6. lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer

Author

Zehua Wang, Bo Yang, Min Zhang, Weiwei Guo, Zhiyuan Wu, Yue Wang, Lin Jia, Song Li, Wen Xie, Da Yang, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Inode Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, SAIC-F-Frederick, Inc, Leidos Biomedical Research, Inc., Wang Z., Yang B., Zhang M., Guo W., Wu Z., Wang Y., Jia L., Li S., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Thorsson V., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein J.N., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., Bruijn I., Gao J., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cherniack A.D., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Meyerson M., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Lazar A.J., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Xie W., and Yang D.

Subjects
0301 basic medicine, breast cancer, CIMP, ENSG00000224271, EPIC1, LOC284930, long noncoding RNA, MYC, P21, TCGA pan-cancer, Cancer Research, PROTEIN, Cancer Genome Atlas Research Network, medicine.disease_cause, ANALYSES REVEAL, Epigenesis, Genetic, Mice, LS2_1, LS4_6, 610 Medicine & health, Promoter Regions, Genetic, GENE-EXPRESSION, Regulation of gene expression, FENÓTIPOS, Cell Cycle, METHYLATION, Cell cycle, Prognosis, Long non-coding RNA, Up-Regulation, TRANSCRIPTIONAL NETWORK, GENOME, Gene Expression Regulation, Neoplastic, SEQ, CpG site, Oncology, DNA methylation, Female, RNA, Long Noncoding, Life Sciences & Biomedicine, Breast Neoplasm, Human, Prognosi, Breast Neoplasms, Biology, BINDING-SITES, Article, NO, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Cell Line, Tumor, medicine, C-MYC, Animals, Humans, 1112 Oncology and Carcinogenesis, Epigenetics, Oncology & Carcinogenesis, Science & Technology, Binding Sites, Animal, Binding Site, Cancer, Cell Biology, DNA Methylation, medicine.disease, 030104 developmental biology, Cancer research, CpG Islands, CpG Island, Carcinogenesis, 1109 Neurosciences, Neoplasm Transplantation
Abstract

We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to the CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation of 1,006 lncRNA genes in cancer, including EPIC1 (epigenetically-induced lncRNA1). Overexpression of EPIC1 is associated with poor prognosis in luminal B breast cancer patients and enhances tumor growth in vitro and in vivo. Mechanistically, EPIC1 promotes cell-cycle progression by interacting with MYC through EPIC1's 129–283 nt region. EPIC1 knockdown reduces the occupancy of MYC to its target genes (e.g., CDKN1A, CCNA2, CDC20, and CDC45). MYC depletion abolishes EPIC1's regulation of MYC target and luminal breast cancer tumorigenesis in vitro and in vivo. Wang et al. characterize the epigenetic landscape of lncRNAs genes across a large number of human tumors and cancer cell lines and observe recurrent hypomethylation of lncRNA genes, including EPIC1. EPIC1 RNA promotes cell-cycle progression by interacting with MYC and enhancing its binding to target genes.

Published
2018

7. The Integrated Genomic Landscape of Thymic Epithelial Tumors

Author

Milan Radovich, Curtis R. Pickering, Ina Felau, Gavin Ha, Hailei Zhang, Heejoon Jo, Katherine A. Hoadley, Pavana Anur, Jiexin Zhang, Mike McLellan, Reanne Bowlby, Thomas Matthew, Ludmila Danilova, Apurva M. Hegde, Jaegil Kim, Mark D.M. Leiserson, Geetika Sethi, Charles Lu, Michael Ryan, Xiaoping Su, Andrew D. Cherniack, Gordon Robertson, Rehan Akbani, Paul Spellman, John N. Weinstein, D. Neil Hayes, Ben Raphael, Tara Lichtenberg, Kristen Leraas, Jean Claude Zenklusen, Junya Fujimoto, Cristovam Scapulatempo-Neto, Andre L. Moreira, David Hwang, James Huang, Mirella Marino, Robert Korst, Giuseppe Giaccone, Yesim Gokmen-Polar, Sunil Badve, Arun Rajan, Philipp Ströbel, Nicolas Girard, Ming S. Tsao, Alexander Marx, Anne S. Tsao, Patrick J. Loehrer, Adrian Ally, Elizabeth L. Appelbaum, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Madhusmita Behera, Rameen Beroukhim, Mario Berrios, Giovanni Blandino, Tom Bodenheimer, Moiz S. Bootwalla, Jay Bowen, Denise Brooks, Flavio M. Carcano, Rebecca Carlsen, Andre L. Carvalho, Patricia Castro, Lara Chalabreysse, Lynda Chin, Juok Cho, Gina Choe, Eric Chuah, Sudha Chudamani, Carrie Cibulskis, Leslie Cope, Matthew G. Cordes, Daniel Crain, Erin Curley, Timothy Defreitas, John A. Demchok, Frank Detterbeck, Noreen Dhalla, Hendrik Dienemann, W. Jeff Edenfield, Francesco Facciolo, Martin L. Ferguson, Scott Frazer, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Stacey B. Gabriel, Johanna Gardner, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, David I. Heiman, Shital Hobensack, Andrea Holbrook, Robert A. Holt, Alan P. Hoyle, Carolyn M. Hutter, Michael Ittmann, Stuart R. Jefferys, Corbin D. Jones, Steven J.M. Jones, Katayoon Kasaian, Patrick K. Kimes, Phillip H. Lai, Peter W. Laird, Michael S. Lawrence, Pei Lin, Jia Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Dennis T. Maglinte, David Mallery, Elaine R. Mardis, Marco A. Marra, Julie Martin, Michael Mayo, Sam Meier, Michael Meister, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Christopher A. Miller, Gordon B. Mills, Richard A. Moore, Scott Morris, Lisle E. Mose, Thomas Muley, Andrew J. Mungall, Karen Mungall, Rashi Naresh, Yulia Newton, Michael S. Noble, Taofeek Owonikoko, Joel S. Parker, Joseph Paulaskis, Robert Penny, Charles M. Perou, Corinne Perrin, Todd Pihl, Amie Radenbaugh, Suresh Ramalingam, Nilsa Ramirez, Ralf Rieker, Jeffrey Roach, Sara Sadeghi, Gordon Saksena, Jacqueline E. Schein, Heather K. Schmidt, Steven E. Schumacher, Candace Shelton, Troy Shelton, Yan Shi, Juliann Shih, Gabriel Sica, Henrique C.S. Silveira, Janae V. Simons, Payal Sipahimalani, Tara Skelly, Heidi J. Sofia, Matthew G. Soloway, Joshua Stuart, Qiang Sun, Angela Tam, Donghui Tan, Roy Tarnuzzer, Nina Thiessen, David J. Van Den Berg, Mohammad A. Vasef, Umadevi Veluvolu, Doug Voet, Vonn Walter, Yunhu Wan, Zhining Wang, Arne Warth, Cleo-Aron Weis, Daniel J. Weisenberger, Matthew D. Wilkerson, Lisa Wise, Tina Wong, Hsin-Ta Wu, Ye Wu, Liming Yang, Jiashan Zhang, and Erik Zmuda

Subjects
Adult, Male, 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Cancer Research, Thymoma, Adolescent, Biology, medicine.disease_cause, Article, Autoimmunity, Transcription Factors, TFII, Young Adult, 03 medical and health sciences, medicine, Humans, Neoplasms, Glandular and Epithelial, HRAS, Thymic carcinoma, Aged, Aged, 80 and over, Autoimmune disease, Oncogene, Genomics, Thymus Neoplasms, Cell Biology, Middle Aged, medicine.disease, Myasthenia gravis, 3. Good health, 030104 developmental biology, Oncology, Mutation, Cancer research, Female
Abstract

Summary Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.

Published
2018

8. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

Author

Benjamin J. Raphael, Ralph H. Hruban, Andrew J. Aguirre, Richard A. Moffitt, Jen Jen Yeh, Chip Stewart, A. Gordon Robertson, Andrew D. Cherniack, Manaswi Gupta, Gad Getz, Stacey B. Gabriel, Matthew Meyerson, Carrie Cibulskis, Suzanne S. Fei, Toshinori Hinoue, Hui Shen, Peter W. Laird, Shiyun Ling, Yiling Lu, Gordon B. Mills, Rehan Akbani, Phillipe Loher, Eric R. Londin, Isidore Rigoutsos, Aristeidis G. Telonis, Ewan A. Gibb, Anna Goldenberg, Aziz M. Mezlini, Katherine A. Hoadley, Eric Collisson, Eric Lander, Bradley A. Murray, Julian Hess, Mara Rosenberg, Louis Bergelson, Hailei Zhang, Juok Cho, Grace Tiao, Jaegil Kim, Dimitri Livitz, Ignaty Leshchiner, Brendan Reardon, Eliezer Van Allen, Atanas Kamburov, Rameen Beroukhim, Gordon Saksena, Steven E. Schumacher, Michael S. Noble, David I. Heiman, Nils Gehlenborg, Michael S. Lawrence, Volkan Adsay, Gloria Petersen, David Klimstra, Nabeel Bardeesy, Mark D.M. Leiserson, Reanne Bowlby, Katayoon Kasaian, Inanc Birol, Karen L. Mungall, Sara Sadeghi, John N. Weinstein, Paul T. Spellman, Yuexin Liu, Laufey T. Amundadottir, Joel Tepper, Aatur D. Singhi, Rajiv Dhir, Drwiega Paul, Thomas Smyrk, Lizhi Zhang, Paula Kim, Jay Bowen, Jessica Frick, Julie M. Gastier-Foster, Mark Gerken, Kevin Lau, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Jeremy Renkel, Mark Sherman, Lisa Wise, Peggy Yena, Erik Zmuda, Juliann Shih, Adrian Ally, Miruna Balasundaram, Rebecca Carlsen, Andy Chu, Eric Chuah, Amanda Clarke, Noreen Dhalla, Robert A. Holt, Steven J.M. Jones, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Denise Brooks, J. Todd Auman, Saianand Balu, Tom Bodenheimer, D. Neil Hayes, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Charles M. Perou, Amy H. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Joel S. Parker, Matthew D. Wilkerson, Anil Korkut, Yasin Senbabaoglu, Patrick Burch, Robert McWilliams, Kari Chaffee, Ann Oberg, Wei Zhang, Marie-Claude Gingras, David A. Wheeler, Liu Xi, Monique Albert, John Bartlett, Harman Sekhon, Yeager Stephen, Zaren Howard, Miller Judy, Anne Breggia, Rachna T. Shroff, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Smith Jennifer, Kevin Roggin, Karl-Friedrich Becker, Madhusmita Behera, Joseph Bennett, Lori Boice, Eric Burks, Carlos Gilberto Carlotti Junior, John Chabot, Daniela Pretti da Cunha Tirapelli, Jose Sebastião dos Santos, Michael Dubina, Jennifer Eschbacher, Mei Huang, Lori Huelsenbeck-Dill, Roger Jenkins, Alexey Karpov, Rafael Kemp, Vladimir Lyadov, Shishir Maithel, Georgy Manikhas, Eric Montgomery, Houtan Noushmehr, Adeboye Osunkoya, Taofeek Owonikoko, Oxana Paklina, Olga Potapova, Suresh Ramalingam, W. Kimryn Rathmell, Kimberly Rieger-Christ, Charles Saller, Galiya Setdikova, Alexey Shabunin, Gabriel Sica, Tao Su, Travis Sullivan, Pat Swanson, Katherine Tarvin, Michael Tavobilov, Leigh B. Thorne, Stefan Urbanski, Olga Voronina, Timothy Wang, Daniel Crain, Erin Curley, Johanna Gardner, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Klaus-Peter Janssen, Oliver Bathe, Nathan Bahary, Julia Slotta-Huspenina, Amber Johns, Hanina Hibshoosh, Rosa F. Hwang, Antonia Sepulveda, Amie Radenbaugh, Stephen B. Baylin, Mario Berrios, Moiz S. Bootwalla, Andrea Holbrook, Phillip H. Lai, Dennis T. Maglinte, Swapna Mahurkar, Timothy J. Triche, David J. Van Den Berg, Daniel J. Weisenberger, Lynda Chin, Raju Kucherlapati, Melanie Kucherlapati, Angeliki Pantazi, Peter Park, Doug Voet, Pei Lin, Scott Frazer, Timothy Defreitas, Sam Meier, Sun Young Kwon, Yong Hoon Kim, Sang-Jae Park, Sung-Sik Han, Seong Hoon Kim, Hark Kim, Emma Furth, Margaret Tempero, Chris Sander, Andrew Biankin, David Chang, Peter Bailey, Anthony Gill, James Kench, Sean Grimmond, Australian Pancreatic Cancer Genome Initiative (APGI, Russell Postier, Rosemary Zuna, Hugues Sicotte, John A. Demchok, Martin L. Ferguson, Carolyn M. Hutter, Kenna R. Mills Shaw, Margi Sheth, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jiashan (Julia) Zhang, Ina Felau, and Jean C. Zenklusen

Subjects
0301 basic medicine, Cancer Research, Proteome, endocrine system diseases, ARID1A, medicine.disease_cause, Article, Epigenesis, Genetic, PBRM1, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, CDKN2A, Pancreatic cancer, microRNA, medicine, GNAS complex locus, Humans, neoplasms, biology, Proteomic Profiling, Gene Expression Profiling, ADENOCARCINOMA, Genomics, Cell Biology, DNA Methylation, medicine.disease, digestive system diseases, 3. Good health, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, 030104 developmental biology, Oncology, Mutation, Cancer research, biology.protein, KRAS, Transcriptome, Carcinoma, Pancreatic Ductal
Abstract

Summary We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS , TP5 3, CDKN2A , SMAD4 , RNF43 , ARID1A , TGFβR2 , GNAS , RREB1 , and PBRM1 . KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS , BRAF , CTNNB1 , and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.

Published
2017

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