Characterisation and outcome of RAC1 mutated melanoma.
Immune checkpoint inhibition
Melanoma
Mutational analysis
RAC1 mutation
Systemic treatment
Targeted therapy
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
23
10
2022
revised:
08
01
2023
accepted:
09
01
2023
pubmed:
12
2
2023
medline:
21
3
2023
entrez:
11
2
2023
Statut:
ppublish
Résumé
Activating hot spot R29S mutations in RAC1, a small GTPase influencing several cellular processes including cell proliferation and cytoskeleton rearrangement, have been reported in up to 9% of sun-exposed melanomas. Clinical characteristics and treatment implications of RAC1 mutations in melanoma remain unclear. We investigated the largest set (n = 64) of RAC1 mutated melanoma patients reported to date, including a retrospective single institution cohort (n = 34) from the University Hospital Essen and a prospective multicentre cohort (n = 30) from the translational study Tissue Registry in Melanoma (TRIM; CA209-578), for patient and tumour characteristics as well as therapy outcomes. From 3037 sequenced melanoma samples screened RAC1 mutations occurred in RAC1 mutated melanomas are rare, mostly of cutaneous origin and frequently harbour concomitant MAP kinase mutations, particularly in NRAS. Patients with advanced disease benefit from systemic treatment with ICI.
Sections du résumé
BACKGROUND
Activating hot spot R29S mutations in RAC1, a small GTPase influencing several cellular processes including cell proliferation and cytoskeleton rearrangement, have been reported in up to 9% of sun-exposed melanomas. Clinical characteristics and treatment implications of RAC1 mutations in melanoma remain unclear.
METHODS
We investigated the largest set (n = 64) of RAC1 mutated melanoma patients reported to date, including a retrospective single institution cohort (n = 34) from the University Hospital Essen and a prospective multicentre cohort (n = 30) from the translational study Tissue Registry in Melanoma (TRIM; CA209-578), for patient and tumour characteristics as well as therapy outcomes.
RESULTS
From 3037 sequenced melanoma samples screened RAC1 mutations occurred in
CONCLUSIONS
RAC1 mutated melanomas are rare, mostly of cutaneous origin and frequently harbour concomitant MAP kinase mutations, particularly in NRAS. Patients with advanced disease benefit from systemic treatment with ICI.
Identifiants
pubmed: 36773463
pii: S0959-8049(23)00017-5
doi: 10.1016/j.ejca.2023.01.009
pii:
doi:
Substances chimiques
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
RAC1 protein, human
0
rac1 GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-10Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.