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BRAF L597 mutations in melanoma are associated with sensitivity to MEK inhibitors.

Paper Id
Dahlman KB,Xia J,Hutchinson K,Ng C,Hucks D,Jia P,Atefi M,Su Z,Branch S,Lyle PL,Hicks DJ,Bozon V,Glaspy JA,Rosen N,Solit DB,Netterville JL,Vnencak-Jones CL,Sosman JA,Ribas A,Zhao Z and Pao W
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
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
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Genes Samples CDS Mutation AA Mutation
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Non-Mutant Genes Gene Id (COSG)
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Non-Mutant Samples Sample Id (COSS)
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Sample Name Mutation Count
This tab shows non coding variant in the selected study/paper [more details]
Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq
This tab shows the copy number variation data for this study. Only variants (classified as gain or loss) are listed. [more details]
CNV Gene Sample Position Minor Allele Copy Number Average Ploidy

1. N/A represents cases where average ploidy value is not available( mostly ICGC samples). For some TCGA samples where minor allele information is not available the average ploidy value could not be calculated.

2. For TCGA samples, Ascat algorithm is used to calculate the average ploidy.

3. For CGP samples, Picnic algorithm is used to calculate the average ploidy.

This tab shows a table of count of samples having gain or loss for all genes [more details]
Gene Gain Samples Loss Samples Samples Tested
This tab shows the fusion mutations observed in this sample [more details]
Gene Sample Name Id Sample(COSS) CDS Mutation Somatic status Zygosity Validated Type