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J Invest Dermatol. 2015 Feb;135(2):508-515. doi: 10.1038/jid.2014.366. Epub 2014 Aug 22.

Beyond BRAF(V600): clinical mutation panel testing by next-generation sequencing in advanced melanoma.

Author information

1
Department of Pathology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
2
Department of Surgical Oncology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
3
Department of Biostatistics, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
4
Department of Melanoma Medical Oncology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
5
Department of Pathology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA; Department of Dermatology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
6
Department of Surgical Oncology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA; Department of Cancer Biology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
7
Department of Melanoma Medical Oncology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA; Department of Systems Biology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
8
Department of Hematopathology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
9
Department of Systems Biology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
10
Department of Experimental Therapeutics, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
11
Department of Surgical Oncology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA; Department of Investigational Cancer Therapeutics, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
12
Department of Melanoma Medical Oncology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA; Department of Systems Biology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA. Electronic address: MDavies@mdanderson.org.

Abstract

The management of melanoma has evolved owing to improved understanding of its molecular drivers. To augment the current understanding of the prevalence, patterns, and associations of mutations in this disease, the results of clinical testing of 699 advanced melanoma patients using a pan-cancer next-generation sequencing (NGS) panel of hotspot regions in 46 genes were reviewed. Mutations were identified in 43 of the 46 genes on the panel. The most common mutations were BRAFV600 (36%), NRAS (21%), TP53 (16%), BRAFNon-V600 (6%), and KIT (4%). Approximately one-third of melanomas had >1 mutation detected, and the number of mutations per tumor was associated with melanoma subtype. Concurrent TP53 mutations were the most frequent events in tumors with BRAFV600 and NRAS mutations. Melanomas with BRAFNon-V600mutations frequently harbored concurrent NRAS mutations (18%), which were rare in tumors with BRAFV600 mutations (1.6%). The prevalence of BRAFV600 and KIT mutations were significantly associated with melanoma subtypes, and BRAFV600 and TP53 mutations were significantly associated with cutaneous primary tumor location. Multiple potential therapeutic targets were identified in metastatic unknown primary and cutaneous melanomas that lacked BRAFV600 and NRAS mutations. These results enrich our understanding of the patterns and clinical associations of oncogenic mutations in melanoma.

Comment in

PMID:
25148578
PMCID:
PMC4289407
DOI:
10.1038/jid.2014.366
[Indexed for MEDLINE]
Free PMC Article

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