Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma
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nihms849815.pdf
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Author(s)
Fishbein, Lauren
Walter, Vonn
Danilova, Ludmila
Robertson, A. Gordon
Johnson, Amy R.
Lichtenberg, Tara M.
Murray, Bradley A.
Ghayee, Hans K.
Else, Tobias
Ling, Shiyun
Date Issued
February 2017
Journal
Cancer Cell
Publisher
Elsevier
Citation
Fishbein, Lauren et al. “Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.” Cancer Cell 31, 2 (February 2017): 181–193 © 2017 Elsevier Inc
Version
Author's final manuscript
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.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CCELL.2017.01.001
