| Literature DB >> 28162975 |
Lauren Fishbein1, Ignaty Leshchiner2, Vonn Walter3, Ludmila Danilova4, A Gordon Robertson5, Amy R Johnson6, Tara M Lichtenberg7, Bradley A Murray2, Hans K Ghayee8, Tobias Else9, Shiyun Ling10, Stuart R Jefferys3, Aguirre A de Cubas11, Brandon Wenz12, Esther Korpershoek13, Antonio L Amelio3, Liza Makowski14, W Kimryn Rathmell11, Anne-Paule Gimenez-Roqueplo15, Thomas J Giordano16, Sylvia L Asa17, Arthur S Tischler18, Karel Pacak19, Katherine L Nathanson20, Matthew D Wilkerson21.
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.Entities:
Keywords: CSDE1; MAML3; TCGA; expression subtypes; genomics; metastasis; molecular profiling; paraganglioma; pheochromocytoma; sequencing
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Year: 2017 PMID： 28162975 PMCID： PMC5643159 DOI： 10.1016/j.ccell.2017.01.001
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743