Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

• Main Authors: Fishbein, Lauren (Author), Walter, Vonn (Author), Danilova, Ludmila (Author), Robertson, A. Gordon (Author), Johnson, Amy R. (Author), Lichtenberg, Tara M. (Author), Murray, Bradley A. (Author), Ghayee, Hans K. (Author), Else, Tobias (Author), Ling, Shiyun (Author), Jefferys, Stuart R. (Author), de Cubas, Aguirre A. (Author), Wenz, Brandon (Author), Korpershoek, Esther (Author), Amelio, Antonio L. (Author), Makowski, Liza (Author), Rathmell, W. Kimryn (Author), Gimenez-Roqueplo (Author), Giordano, Thomas J. (Author), Asa, Sylvia L. (Author), Tischler, Arthur S. (Author), Pacak, Karel (Author), Nathanson, Katherine L. (Author), Wilkerson, Matthew D. (Author), Akbani, Rehan (Author), Ally, Adrian (Author), Amar, Laurence (Author), Arachchi, Harindra (Author), Auchus, Richard J. (Author), Auman, J. Todd (Author), Baertsch, Robert (Author), Balasundaram, Miruna (Author), Balu, Saianand (Author), Bartsch, Detlef K. (Author), Baudin, Eric (Author), Bauer, Thomas (Author), Beaver, Allison (Author), Benz, Christopher (Author), Beroukhim, Rameen (Author), Beuschlein, Felix (Author), Bodenheimer, Tom (Author), Boice, Lori (Author), Bowlby, Reanne (Author), Brooks, Denise (Author), Carlsen, Rebecca (Author), Carter, Suzie (Author), Cassol, Clarissa A. (Author), Cherniack, Andrew D. (Author), Chin, Lynda (Author), Cho, Juok (Author), Chuah, Eric (Author), Chudamani, Sudha (Author), Cope, Leslie (Author), Crain, Daniel (Author), Curley, Erin (Author), de Krijger, Ronald R. (Author), Demchok, John A. (Author), Deutschbein, Timo (Author), Dhalla, Noreen (Author), Dimmock, David (Author), Dinjens, Winand N.M (Author), Eng, Charis (Author), Eschbacher, Jennifer (Author), Fassnacht, Martin (Author), Felau, Ina (Author), Feldman, Michael (Author), Ferguson, Martin L. (Author), Fiddes, Ian (Author), Frazer, Scott (Author), Gabriel, Stacey B. (Author), Gardner, Johanna (Author), Gastier-Foster, Julie M. (Author), Gehlenborg, Nils (Author), Gerken, Mark (Author), Getz, Gad (Author), Geurts, Jennifer (Author), Goldman, Mary (Author), Graim, Kiley (Author), Gupta, Manaswi (Author), Haan, David (Author), Hahner, Stefanie (Author), Hantel, Constanze (Author), Haussler, David (Author), Hayes, D. Neil (Author), Heiman, David I. (Author), Hoadley, Katherine A. (Author), Holt, Robert A. (Author), Hoyle, Alan P. (Author), Huang, Mei (Author), Hunt, Bryan (Author), Hutter, Carolyn M. (Author), Jones, Steven J.M (Author), Jones, Corbin D. (Author), Kasaian, Katayoon (Author), Kebebew, Electron (Author), Kim, Jaegil (Author), Kimes, Patrick (Author), Knijnenburg, Theo (Author), Lander, Eric (Author), Lawrence, Michael S. (Author), Lechan, Ronald (Author), Lee, Darlene (Author), Leraas, Kristen M. (Author), Lerario, Antonio (Author), Lin, Pei (Author), Liu, Jia (Author), LiVolsi, Virginia A. (Author), Lolla, Laxmi (Author), Lotan, Yair (Author), Lu, Yiling (Author), Ma, Yussanne (Author), Maison, Nicole (Author), Mallery, David (Author), Mannelli, Massimo (Author), Marquard, Jessica (Author), Marra, Marco A. (Author), Matthew, Thomas (Author), Mayo, Michael (Author), Méatchi, Tchao (Author), Meng, Shaowu (Author), Merino, Maria J. (Author), Mete, Ozgur (Author), Meyerson, Matthew (Author), Mieczkowski, Piotr A. (Author), Mills, Gordon B. (Author), Moore, Richard A. (Author), Morozova, Olena (Author), Morris, Scott (Author), Mose, Lisle E. (Author), Mungall, Andrew J. (Author), Naresh, Rashi (Author), Newton, Yulia (Author), Ng, Sam (Author), Ni, Ying (Author), Noble, Michael S. (Author), Nwariaku, Fiemu (Author), Parker, Joel S. (Author), Paul, Evan (Author), Penny, Robert (Author), Perou, Charles M. (Author), Perou, Amy H. (Author), Pihl, Todd (Author), Powers, James (Author), Rabaglia, Jennifer (Author), Radenbaugh, Amie (Author), Ramirez, Nilsa C. (Author), Rao, Arjun (Author), Riester, Anna (Author), Roach, Jeffrey (Author), Sadeghi, Sara (Author), Saksena, Gordon (Author), Salama, Sofie (Author), Saller, Charles (Author), Sandusky, George (Author), Sbiera, Silviu (Author), Schein, Jacqueline E. (Author), Schumacher, Steven E. (Author), Shelton, Candace (Author), Shelton, Troy (Author), Sheth, Margi (Author), Shi, Yan (Author), Shih, Juliann (Author), Shmulevich, Ilya (Author), Simons, Janae V. (Author), Sipahimalani, Payal (Author), Skelly, Tara (Author), Sofia, Heidi J. (Author), Sokolov, Artem (Author), Soloway, Matthew G. (Author), Sougnez, Carrie (Author), Stuart, Josh (Author), Sun, Charlie (Author), Swatloski, Teresa (Author), Tam, Angela (Author), Tan, Donghui (Author), Tarnuzzer, Roy (Author), Tarvin, Katherine (Author), Thiessen, Nina (Author), Thorne, Leigh B. (Author), Timmers, Henri J. (Author), Tse, Kane (Author), Uzunangelov, Vlado (Author), van Berkel, Anouk (Author), Veluvolu, Umadevi (Author), Vicha, Ales (Author), Voet, Doug (Author), Waldmann, Jens (Author), Wan, Yunhu (Author), Wang, Zhining (Author), Wang, Tracy S. (Author), Weaver, Joellen (Author), Weinstein, John N. (Author), Weismann, Dirk (Author), Wise, Lisa (Author), Wong, Tina (Author), Wu, Ye (Author), Yang, Liming (Author), Zelinka, Tomas (Author), Zenklusen, Jean C. (Author), Zhang, Jiashan (Julia) (Author), Zhang, Wei (Author), Zhu, Jingchun (Author), Zinzindohoué, Franck (Author), Zmuda, Erik (Author), Leshchiner, Ignaty (Contributor), Lander, Eric Steven (Contributor), Wong, Christopher, M. Eng. Massachusetts Institute of Technology (Author)
• Other Authors: Broad Institute of MIT and Harvard (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2018-06-29T18:33:12Z.
• Subjects: Article
• Online Access: Get fulltext

We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.
National Institutes of Health (U.S.) (Grant U54HG003273)
National Institutes of Health (U.S.) (Grant U54HG003067)
National Institutes of Health (U.S.) (Grant U54HG003079)
National Institutes of Health (U.S.) (Grant U24CA143799)
National Institutes of Health (U.S.) (Grant U24CA143835)
National Institutes of Health (U.S.) (Grant U24CA143840)
National Institutes of Health (U.S.) (Grant U24CA143843)
National Institutes of Health (U.S.) (Grant U24CA143845)
National Institutes of Health (U.S.) (Grant U24CA143848)
National Institutes of Health (U.S.) (Grant U24CA143858)
National Institutes of Health (U.S.) (Grant U24CA143866)
National Institutes of Health (U.S.) (Grant U24CA143867)
National Institutes of Health (U.S.) (Grant U24CA143882)
National Institutes of Health (U.S.) (Grant U24CA143883)
National Institutes of Health (U.S.) (Grant U24CA144025)
National Institutes of Health (U.S.) (Grant P30CA016672)