Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.
| Authors | Lauren Fishbein, Ignaty Leshchiner, Vonn Walter, Ludmila Danilova, A Gordon Robertson, Amy R Johnson, Tara M Lichtenberg, Bradley A Murray, Hans K Ghayee, Tobias Else, Shiyun Ling, Stuart R Jefferys, Aguirre A de Cubas, Brandon Wenz, Esther Korpershoek, Antonio L Amelio, Liza Makowski, W Kimryn Rathmell, Anne-Paule Gimenez-Roqueplo, Thomas J Giordano, Sylvia L Asa, Arthur S Tischler, Cancer Genome Atlas Research Network, Karel Pacak, Katherine L Nathanson & Matthew D Wilkerson |
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| 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. |
| Journal Name and Citation | Cancer Cell. 2017 Feb 13;31(2):181-193. |
| Date of Publication | 2017/02/02 |
| Publication Link | http://www.sciencedirect.com/science/article/pii/S1535610817300016 |