Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling.
CRKL
MYC
NF2
acral
dasatinib
fusions
melanoma
mucosal
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
12 Jul 2024
12 Jul 2024
Historique:
revised:
27
10
2021
received:
21
12
2020
accepted:
29
10
2021
medline:
13
7
2024
pubmed:
13
7
2024
entrez:
13
7
2024
Statut:
aheadofprint
Résumé
Despite advancements in treating cutaneous melanoma, patients with acral and mucosal (A/M) melanomas still have limited therapeutic options and poor prognoses. We analyzed 156 melanomas (101 cutaneous, 28 acral, and 27 mucosal) using the Foundation One cancer-gene specific clinical testing platform and identified new, potentially targetable genomic alterations (GAs) in specific anatomic sites of A/M melanomas. Using novel pre-clinical models of A/M melanoma, we demonstrate that several GAs and corresponding oncogenic pathways associated with cutaneous melanomas are similarly targetable in A/M melanomas. Other alterations, including MYC and CRKL amplifications, were unique to A/M melanomas and susceptible to indirect targeting using the BRD4 inhibitor JQ1 or Src/ABL inhibitor dasatinib, respectively. We further identified new, actionable A/M-specific alterations, including an inactivating NF2 fusion in a mucosal melanoma responsive to dasatinib in vivo. Our study highlights new molecular differences between cutaneous and A/M melanomas, and across different anatomic sites within A/M, which may change clinical testing and treatment paradigms for these rare melanomas.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Moore Family Foundation
Organisme : Patten-Davis Foundation
Organisme : NCI NIH HHS
ID : NIH/NCI CCSG P30CA046934
Pays : United States
Organisme : American Cancer Society
ID : IRG-16-184-56
Organisme : Paul R. Ohara II Seed Grant Program
Informations de copyright
© 2024 UICC.
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