Recurrent hotspot SF3B1 mutations at codon 625 in vulvovaginal mucosal melanoma identified in a study of 27 Australian mucosal melanomas.

Oncotarget 2019 Jan 29;10(9):930-941. Epub 2019 Jan 29.

Melanoma Institute Australia, The University of Sydney, Sydney, Australia.

Introduction: Clinical outcomes for mucosal melanomas are often poor due to a lack of effective systemic drug therapies. Identifying driver genes in mucosal melanoma may enhance the understanding of disease pathogenesis and provide novel opportunities to develop effective therapies.

Results: Somatic variant analysis identified (6 of 27: 22%) as the most commonly mutated gene, followed by (3 of 27: 11%). Other less frequently mutated genes (4% otherwise stated) included (7%), (7%), , , , , , , and . Recurrent SF3B1 p.R625 hotspot mutations were exclusively detected in vulvovaginal (5 of 19: 26%) and anorectal melanomas (3 of 5:60%). The only other SF3B1 mutation was a p.C1123Y mutation that occurred in a conjunctival mucosal melanoma.-mutated patients were associated with shorter overall survival (OS; 34.9 months) and progression-free survival (PFS; 16.9 months) compared to non--mutated patients (OS: 79.7 months, log-rank = 0.1172; PFS: 35.7 months, log-rank = 0.0963).

Conclusion: Molecular subgroups of mucosal melanoma with mutations occurred predominantly in the vulvovaginal region. mutations may have a negative prognostic impact.

Methods: Formalin-fixed biopsies were collected from 27 pathologically-confirmed mucosal melanomas. Genomic DNA was isolated from the tumor tissue and sequenced using a novel dual-strand amplicon sequencing technique to determine the frequency and types of mutations across 45 target genes.

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http://dx.doi.org/10.18632/oncotarget.26584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398173PMC
January 2019
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