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

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

Publication date: Jan 29, 2019

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.

Somatic variant analysis identified SF3B1 (6 of 27: 22%) as the most commonly mutated gene, followed by KIT (3 of 27: 11%). Other less frequently mutated genes (4% otherwise stated) included BRAF (7%), NRAS (7%), ARID2, CTNNB1, DICER1, MAP2K1, NF1, PTEN, SETD2 and TP53. 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.SF3B1-mutated patients were associated with shorter overall survival (OS; 34.9 months) and progression-free survival (PFS; 16.9 months) compared to non-SF3B1-mutated patients (OS: 79.7 months, log-rank P = 0.1172; PFS: 35.7 months, log-rank P = 0.0963).

Molecular subgroups of mucosal melanoma with SF3B1 mutations occurred predominantly in the vulvovaginal region. SF3B1 mutations may have a negative prognostic impact.

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.

Quek, C., Rawson, R.V., Ferguson, P.M., Shang, P., , Silva, Saw, R.P.M., Shannon, K., Thompson, J.F., Hayward, N.K., Long, G.V., Mann, G.J., Scolyer, R.A., and Wilmott, J.S. Recurrent hotspot SF3B1 mutations at codon 625 in vulvovaginal mucosal melanoma identified in a study of 27 Australian mucosal melanomas. 22034. 2019 Oncotarget (10):9.

Concepts Keywords
Amplicon Articles
Biopsies Progression-free survival
BRAF BRAF
Codon Mucosal melanoma
Conjunctival Health
CTNNB1 SF3B1
DICER1 RTT
Formalin Cancer
Frequency Rare diseases
Gene Medicine
Hotspot Melanoma
KIT Drug therapies
Melanomas Driver mucosal melanoma
Mutation Tumor
NF1 Vulvovaginal mucosal melanoma
Pathogenesis Anorectal melanomas
PTEN
Sequencing
TP53
Tumor

Semantics

Type Source Name
disease MESH tumor
drug DRUGBANK Formaldehyde
gene UNIPROT IMPACT
gene UNIPROT TNFRSF11A
gene UNIPROT TP53
gene UNIPROT SETD2
gene UNIPROT PTEN
gene UNIPROT NF1
gene UNIPROT MAP2K1
gene UNIPROT DICER1
gene UNIPROT CTNNB1
gene UNIPROT ARID2
gene UNIPROT NRAS
gene UNIPROT BRAF
gene UNIPROT KIT
disease MESH melanomas
disease DOID mucosal melanoma
gene UNIPROT SF3B1
gene UNIPROT SF3B2

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