Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.
Authors | |
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. |
Year of Publication | 2017
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Journal | Cancer Cell
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Volume | 31
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Issue | 2
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Pages | 181-193
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Date Published | 2017 Feb 13
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ISSN | 1878-3686
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DOI | 10.1016/j.ccell.2017.01.001
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PubMed ID | 28162975
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Links | |
Grant list | U24 CA143882 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
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