학술논문
Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.
Document Type
Article
Author
Fishbein, Lauren; Leshchiner, Ignaty; Walter, Vonn; Danilova, Ludmila; Robertson, A. Gordon; Johnson, Amy R.; Lichtenberg, Tara M.; Murray, Bradley A.; Ghayee, Hans K.; Else, Tobias; Ling, Shiyun; Jefferys, Stuart R.; de Cubas, Aguirre A.; Wenz, Brandon; Korpershoek, Esther; Amelio, Antonio L.; Makowski, Liza; Rathmell, W. Kimryn; Gimenez-Roqueplo, Anne-Paule; Giordano, Thomas J.
Source
Subject
*PHEOCHROMOCYTOMA
*PARAGANGLIOMA
*MOLECULAR oncology
*GENETIC mutation
*CANCER genetics
*INDIVIDUALIZED medicine
*
*
*
*
*
Language
ISSN
1535-6108
Abstract
Summary 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. [ABSTRACT FROM AUTHOR]