Comprehensive molecular characterization of pheochromocytoma and paraganglioma

By Lauren Fishbein, I. Leshchiner, Vonn Walter, Ludmila V. Danilova, A. G. Robertson, A. Johnson, T. Lichtenberg, Bradley A. Murray, H. Ghayee, T. Else and 15 more. Cancer Cell, 2017

670 citations recorded by the source corpus.

Summary We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCC/PGLs), a rare tumor type. Multi-platform integration revealed that PCC/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, NF1). We also discovered fusion genes in PCC/PGL, involving MAML3, BRAF, NGFR and NF1. Integrated analysis classified PCC/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 PCC/PGL included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

Subfields: Cancer Research, Endocrinology, Diabetes and Metabolism, Surgery

View Paper: https://www.semanticscholar.org/paper/eafdfd9ae95f80fd4ec66df5dd811d5368a3dff8