Whole-exome sequencing identifies recurrent SF3B1 R625 mutation and comutation of NF1 and KIT in mucosal melanoma

Jennifer D. Hintzsche, Nicholas T. Gorden, Carol M. Amato, Jihye Kim, Kelsey E. Wuensch, Steven E. Robinson, Allison J. Applegate, Kasey L. Couts, Theresa M. Medina, Keith R. Wells, Joshua A. Wisell, Martin D. McCarter, Neil F. Box, Yiqun G. Shellman, Rene C. Gonzalez, Karl D. Lewis, John J. Tentler, Aik Choon Tan, William A. Robinson

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)189-199
Number of pages11
JournalMelanoma Research
Issue number3
Publication statusPublished - 2017

Bibliographical note

Funding Information:
This work is partly supported by the National Institutes of Health P30CA046934, Cancer League of Colorado, the David F. and Margaret T. Grohne Family Foundation, the Rifkin Endowed Chair (WAR), the Amy Davis Foundation and the Moore Family Foundation

Publisher Copyright:
© 2017 The Author(s). Published by Wolters Kluwer Health, Inc.


  • SF3B1 mutation
  • genomic landscape
  • mucosal melanoma
  • spliceosome
  • whole-exome sequencing

ASJC Scopus subject areas

  • Oncology
  • Dermatology
  • Cancer Research


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