Oncogenic Signaling Pathways in The Cancer Genome Atlas

Francisco Sanchez-Vega; Marco Mina; Joshua Armenia; Walid K Chatila; Augustin Luna; Konnor C La; Sofia Dimitriadoy; David L Liu; Havish S Kantheti; Sadegh Saghafinia; Debyani Chakravarty; Foysal Daian; Qingsong Gao; Matthew H Bailey; Wen-Wei Liang; Steven M Foltz; Ilya Shmulevich; Li Ding; Zachary Heins; Angelica Ochoa; Benjamin Gross; Jianjiong Gao; Hongxin Zhang; Ritika Kundra; Cyriac Kandoth; Istemi Bahceci; Leonard Dervishi; Ugur Dogrusoz; Wanding Zhou; Hui Shen; Peter W Laird; Gregory P Way; Casey S Greene; Han Liang; Yonghong Xiao; Chen Wang; Antonio Iavarone; Alice H Berger; Trever G Bivona; Alexander J Lazar; Gary D Hammer; Thomas Giordano; Lawrence N Kwong; Grant McArthur; Chenfei Huang; Aaron D Tward; Mitchell J Frederick; Frank McCormick; Matthew Meyerson; Cancer Genome Atlas Research Network; Eliezer M Van Allen; Andrew D Cherniack; Giovanni Ciriello; Chris Sander; Nikolaus Schultz

doi:10.1016/j.cell.2018.03.035

Oncogenic Signaling Pathways in The Cancer Genome Atlas

Cell. 2018 Apr 5;173(2):321-337.e10. doi: 10.1016/j.cell.2018.03.035.

Authors

Francisco Sanchez-Vega¹, Marco Mina², Joshua Armenia¹, Walid K Chatila³, Augustin Luna⁴, Konnor C La³, Sofia Dimitriadoy⁵, David L Liu⁶, Havish S Kantheti⁷, Sadegh Saghafinia², Debyani Chakravarty³, Foysal Daian³, Qingsong Gao⁸, Matthew H Bailey⁸, Wen-Wei Liang⁸, Steven M Foltz⁸, Ilya Shmulevich⁹, Li Ding¹⁰, Zachary Heins³, Angelica Ochoa³, Benjamin Gross³, Jianjiong Gao³, Hongxin Zhang³, Ritika Kundra³, Cyriac Kandoth³, Istemi Bahceci¹¹, Leonard Dervishi¹¹, Ugur Dogrusoz¹¹, Wanding Zhou¹², Hui Shen¹², Peter W Laird¹², Gregory P Way¹³, Casey S Greene¹³, Han Liang¹⁴, Yonghong Xiao¹⁵, Chen Wang¹⁶, Antonio Iavarone¹⁷, Alice H Berger¹⁸, Trever G Bivona¹⁹, Alexander J Lazar²⁰, Gary D Hammer²¹, Thomas Giordano²², Lawrence N Kwong²³, Grant McArthur²⁴, Chenfei Huang²⁵, Aaron D Tward²⁶, Mitchell J Frederick²⁵, Frank McCormick²⁷, Matthew Meyerson⁶; Cancer Genome Atlas Research Network; Eliezer M Van Allen⁶, Andrew D Cherniack⁶, Giovanni Ciriello²⁸, Chris Sander²⁹, Nikolaus Schultz³⁰

Collaborators

Cancer Genome Atlas Research Network:
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, Ino de 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 Jr, 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

Affiliations

¹ Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
² Department of Computational Biology, University of Lausanne (UNIL), 1011 Lausanne, Vaud, Switzerland and Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
³ Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁴ cBio Center, Dana-Farber Cancer Institute, Boston, MA; Department of Cell Biology, Harvard Medical School, Boston, MA.
⁵ Princeton University, Princeton, NJ, USA.
⁶ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, US.
⁷ University of Texas at Dallas, Richardson, TX 75080, USA.
⁸ Department of Medicine and McDonnell Genome Institute, Washington University in St. Louis, St. Louis, Missouri, 63110, USA.
⁹ Institute for Systems Biology, Seattle, WA, USA.
¹⁰ Department of Medicine and McDonnell Genome Institute, Washington University in St. Louis, St. Louis, Missouri, 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
¹¹ Computer Engineering Department, Bilkent University, Ankara 06800, Turkey.
¹² Van Andel Research Institute, 333 Bostwick Ave NE, Grand Rapids Michigan, 49503, USA.
¹³ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
¹⁴ Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁵ TESARO Inc., Waltham, MA, 02451, USA.
¹⁶ Department of Health Sciences Research and Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
¹⁷ Institute for Cancer Genetics, Department of Neurology and Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA.
¹⁸ Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
¹⁹ UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, California 94143, USA.
²⁰ Departments of Pathology, Genomic Medicine & Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd-Unit 85, Houston, Texas 77030, USA.
²¹ Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, Endocrine Oncology Program, University of Michigan, Ann Arbor, Michigan, MI 48105, USA.
²² Department of Pathology, University of Michigan Medical School, Ann Arbor, MI; Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, MI; Comprehensive Cancer Center, Michigan Medicine, Ann Arbor, MI, USA.
²³ Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁴ Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia.
²⁵ Dept. of Otolaryngology, Baylor College of Medicine, USA.
²⁶ University of California, San Francisco Department of Otolaryngology-Head and Neck Surgery. 2233 Post Street, San Francisco, CA, 94143, USA.
²⁷ UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, CA 94143, USA.
²⁸ Department of Computational Biology, University of Lausanne (UNIL), 1011 Lausanne, Vaud, Switzerland and Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland. Electronic address: [email protected].
²⁹ cBio Center, Dana-Farber Cancer Institute, Boston, MA; Department of Cell Biology, Harvard Medical School, Boston, MA. Electronic address: [email protected].
³⁰ Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Departments of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: [email protected].

Abstract

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy.

Keywords: PanCanAtlas; TCGA; cancer genome atlas; cancer genomics; combination therapy; pan-cancer; precision oncology; signaling pathways; therapeutics; whole exome sequencing.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Databases, Genetic*
Genes, Neoplasm
Humans
Neoplasms / genetics
Neoplasms / pathology*
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism
Signal Transduction / genetics*
Transforming Growth Factor beta / genetics
Transforming Growth Factor beta / metabolism
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism
Wnt Proteins / genetics
Wnt Proteins / metabolism

Substances

Transforming Growth Factor beta
Tumor Suppressor Protein p53
Wnt Proteins
Phosphatidylinositol 3-Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding