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.
Original language | English (US) |
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Pages (from-to) | 181-193 |
Number of pages | 13 |
Journal | Cancer cell |
Volume | 31 |
Issue number | 2 |
DOIs | |
State | Published - Feb 13 2017 |
Keywords
- CSDE1
- MAML3
- TCGA
- expression subtypes
- genomics
- metastasis
- molecular profiling
- paraganglioma
- pheochromocytoma
- sequencing
ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research
MD Anderson CCSG core facilities
- Bioinformatics Shared Resource
- Functional Proteomics Reverse Phase Protein Array Core