Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets.
Biomarkers, Tumor
/ genetics
Cyclin-Dependent Kinase 4
/ genetics
DNA Copy Number Variations
/ genetics
Female
Humans
Male
Melanocytes
/ pathology
Melanoma
/ genetics
Point Mutation
/ genetics
Proto-Oncogene Proteins c-mdm2
/ genetics
Signal Transduction
/ genetics
Telomerase
/ genetics
Whole Genome Sequencing
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 07 2019
18 07 2019
Historique:
received:
06
12
2018
accepted:
18
06
2019
entrez:
20
7
2019
pubmed:
20
7
2019
medline:
18
12
2019
Statut:
epublish
Résumé
Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and high numbers of structural variants, including recurrent structural rearrangements targeting TERT, CDK4 and MDM2. Significantly mutated genes are NRAS, BRAF, NF1, KIT, SF3B1, TP53, SPRED1, ATRX, HLA-A and CHD8. SF3B1 mutations occur more commonly in female genital and anorectal melanomas and CTNNB1 mutations implicate a role for WNT signaling defects in the genesis of some mucosal melanomas. TERT aberrations and ATRX mutations are associated with alterations in telomere length. Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors.
Identifiants
pubmed: 31320640
doi: 10.1038/s41467-019-11107-x
pii: 10.1038/s41467-019-11107-x
pmc: PMC6639323
doi:
Substances chimiques
Biomarkers, Tumor
0
MDM2 protein, human
EC 2.3.2.27
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
CDK4 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 4
EC 2.7.11.22
TERT protein, human
EC 2.7.7.49
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3163Subventions
Organisme : Cancer Research UK
ID : 14356
Pays : United Kingdom
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