This section shows a general overview of information for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- BRAF L597 mutations in melanoma are associated with sensitivity to MEK inhibitors.
- Paper ID
- 1Vanderbilt-Ingram Cancer Center, Departments of 2Cancer Biology, 3Biomedical Informatics, 4Pathology, Microbiology, and Immunology, and 5Medicine/Division of Hematology-Oncology, Vanderbilt University School of Medicine; Departments of 6Otolaryngology and 7Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; 8Department of Medicine, Division of Hematology-Oncology, 9Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California;10Program in Molecular Pharmacology and Chemistry, 11Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; 12Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts.
Cancer discovery, 2012;2(9):791-797
PMID: 22798288 (view at PubMed or Europe PMC)
- Kinase inhibitors are accepted treatment for metastatic melanomas that harbor specific driver mutations in BRAF or KIT, but only 40% to 50% of cases are positive. To uncover other potential targetable mutations, we conducted whole-genome sequencing of a highly aggressive BRAF (V600) and KIT (W557, V559, L576, K642, and D816) wild-type melanoma. Surprisingly, we found a somatic BRAF(L597R) mutation in exon 15. Analysis of BRAF exon 15 in 49 tumors negative for BRAF(V600) mutations as well as driver mutations in KIT, NRAS, GNAQ, and GNA11, showed that two (4%) harbored L597 mutations and another two involved BRAF D594 and K601 mutations. In vitro signaling induced by L597R/S/Q mutants was suppressed by mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibition. A patient with BRAF(L597S) mutant metastatic melanoma responded significantly to treatment with the MEK inhibitor, TAK-733. Collectively, these data show clinical significance to BRAF(L597) mutations in melanoma.
- Paper Status
- Genes Analysed
- Mutated Samples
- Total No. of Samples