The distribution of BRAF gene fusions in solid tumors and response to targeted therapy.

Autor: Ross JS; Foundation Medicine, Inc., Cambridge, MA.; Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY., Wang K; Foundation Medicine, Inc., Cambridge, MA., Chmielecki J; Foundation Medicine, Inc., Cambridge, MA., Gay L; Foundation Medicine, Inc., Cambridge, MA., Johnson A; Foundation Medicine, Inc., Cambridge, MA., Chudnovsky J; Foundation Medicine, Inc., Cambridge, MA., Yelensky R; Foundation Medicine, Inc., Cambridge, MA., Lipson D; Foundation Medicine, Inc., Cambridge, MA., Ali SM; Foundation Medicine, Inc., Cambridge, MA., Elvin JA; Foundation Medicine, Inc., Cambridge, MA., Vergilio JA; Foundation Medicine, Inc., Cambridge, MA., Roels S; Foundation Medicine, Inc., Cambridge, MA., Miller VA; Foundation Medicine, Inc., Cambridge, MA., Nakamura BN; Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA., Gray A; Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA., Wong MK; Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA., Stephens PJ; Foundation Medicine, Inc., Cambridge, MA.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2016 Feb 15; Vol. 138 (4), pp. 881-90. Date of Electronic Publication: 2015 Sep 08.
DOI: 10.1002/ijc.29825
Abstrakt: Although the BRAF V600E base substitution is an approved target for the BRAF inhibitors in melanoma, BRAF gene fusions have not been investigated as anticancer drug targets. In our study, a wide variety of tumors underwent comprehensive genomic profiling for hundreds of known cancer genes using the FoundationOne™ or FoundationOne Heme™ comprehensive genomic profiling assays. BRAF fusions involving the intact in-frame BRAF kinase domain were observed in 55 (0.3%) of 20,573 tumors, across 12 distinct tumor types, including 20 novel BRAF fusions. These comprised 29 unique 5' fusion partners, of which 31% (9) were known and 69% (20) were novel. BRAF fusions included 3% (14/531) of melanomas; 2% (15/701) of gliomas; 1.0% (3/294) of thyroid cancers; 0.3% (3/1,062) pancreatic carcinomas; 0.2% (8/4,013) nonsmall-cell lung cancers and 0.2% (4/2,154) of colorectal cancers, and were enriched in pilocytic (30%) vs. nonpilocytic gliomas (1%; p < 0.0001), Spitzoid (75%) vs. nonSpitzoid melanomas (1%; p = 0.0001), acinar (67%) vs. nonacinar pancreatic cancers (<1%; p < 0.0001) and papillary (3%) vs. nonpapillary thyroid cancers (0%; p < 0.03). Clinical responses to trametinib and sorafenib are presented. In conclusion, BRAF fusions are rare driver alterations in a wide variety of malignant neoplasms, but enriched in Spitzoid melanoma, pilocytic astrocytomas, pancreatic acinar and papillary thyroid cancers.
(© 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.)
Databáze: MEDLINE
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