학술논문
Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma
Document Type
article
Author
Fishbein, Lauren; Leshchiner, Ignaty; Walter, Vonn; Danilova, Ludmila; Robertson, A Gordon; Johnson, Amy R; Lichtenberg, Tara M; Murray, Bradley A; Ghayee, Hans K; Else, Tobias; Ling, Shiyun; Jefferys, Stuart R; de Cubas, Aguirre A; Wenz, Brandon; Korpershoek, Esther; Amelio, Antonio L; Makowski, Liza; Rathmell, W Kimryn; Gimenez-Roqueplo, Anne-Paule; Giordano, Thomas J; Asa, Sylvia L; Tischler, Arthur S; Network, The Cancer Genome Atlas Research; Akbani, Rehan; Ally, Adrian; Amar, Laurence; Arachchi, Harindra; Auchus, Richard J; Auman, J Todd; Baertsch, Robert; Balasundaram, Miruna; Balu, Saianand; Bartsch, Detlef K; Baudin, Eric; Bauer, Thomas; Beaver, Allison; Benz, Christopher; Beroukhim, Rameen; Beuschlein, Felix; Bodenheimer, Tom; Boice, Lori; Bowen, Jay; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Carter, Suzie; Cassol, Clarissa A; Cherniack, Andrew D; Chin, Lynda; Cho, Juok; Chuah, Eric; Chudamani, Sudha; Cope, Leslie; Crain, Daniel; Curley, Erin; de Krijger, Ronald R; Demchok, John A; Deutschbein, Timo; Dhalla, Noreen; Dimmock, David; Dinjens, Winand NM; Eng, Charis; Eschbacher, Jennifer; Fassnacht, Martin; Felau, Ina; Feldman, Michael; Ferguson, Martin L; Fiddes, Ian; Frazer, Scott; Gabriel, Stacey B; Gardner, Johanna; Gastier-Foster, Julie M; Gehlenborg, Nils; Gerken, Mark; Getz, Gad; Geurts, Jennifer; Goldman, Mary; Graim, Kiley; Gupta, Manaswi; Haan, David; Hahner, Stefanie; Hantel, Constanze; Haussler, David; Hayes, D Neil; Heiman, David I; Hoadley, Katherine A; Holt, Robert A; Hoyle, Alan P; Huang, Mei; Hunt, Bryan; Hutter, Carolyn M
Source
Cancer Cell. 31(2)
Subject
Language
Abstract
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.