GRCh37 · COSMIC v94

Summary

This section shows a summary 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.

Reference
Whole-exome sequencing identifies recurrent SF3B1 R625 mutation and comutation of NF1 and KIT in mucosal melanoma.
Paper ID
COSP43248
Authors
Hintzsche JD, Gorden NT, Amato CM, Kim J, Wuensch KE, Robinson SE, Applegate AJ, Couts KL, Medina TM, Wells KR, Wisell JA, McCarter MD, Box NF, Shellman YG, Gonzalez RC, Lewis KD, Tentler JJ, Tan AC and Robinson WA
Affiliation
aDepartment of Medicine, Division of Medical Oncology bDepartment of Pathology cDepartment of Surgery, School of Medicine dDepartment of Biostatistics and Informatics, Colorado School of Public Health eUniversity of Colorado Cancer Center fDepartment of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Journal
Melanoma research, 2017
ISSN: 1473-5636
PMID: 28296713 (view at PubMed or Europe PMC)
Abstract
Mucosal melanomas are a rare subtype of melanoma, arising in mucosal tissues, which have a very poor prognosis due to the lack of effective targeted therapies. This study aimed to better understand the molecular landscape of these cancers and find potential new therapeutic targets. Whole-exome sequencing was performed on mucosal melanomas from 19 patients and 135 sun-exposed cutaneous melanomas, with matched peripheral blood samples when available. Mutational profiles were compared between mucosal subgroups and sun-exposed cutaneous melanomas. Comparisons of molecular profiles identified 161 genes enriched in mucosal melanoma (P<0.05). KIT and NF1 were frequently comutated (32%) in the mucosal subgroup, with a significantly higher incidence than that in cutaneous melanoma (4%). Recurrent SF3B1 R625H/S/C mutations were identified and validated in 7 of 19 (37%) mucosal melanoma patients. Mutations in the spliceosome pathway were found to be enriched in mucosal melanomas when compared with cutaneous melanomas. Alternative splicing in four genes were observed in SF3B1-mutant samples compared with the wild-type samples. This study identified potential new therapeutic targets for mucosal melanoma, including comutation of NF1 and KIT, and recurrent R625 mutations in SF3B1. This is the first report of SF3B1 R625 mutations in vulvovaginal mucosal melanoma, with the largest whole-exome sequencing project of mucosal melanomas to date. The results here also indicated that the mutations in SF3B1 lead to alternative splicing in multiple genes. These findings expand our knowledge of this rare disease.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.
Paper Status
Curated