Definition of biologically distinct groups of conjunctival melanomas according to etiological factors and implications for precision medicine
Stern, M. H
AffiliationINSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée par la Ligue Nationale Contre le Cancer and PSL Research University, Department of Biopathology, Institut Curie, PSL Research University, F-75005 Paris, France
MetadataShow full item record
AbstractConjunctival melanoma (ConjMel) is a potentially deadly ocular melanoma, originating from partially sunlight-exposed mucosa. We explored the mutational landscape of ConjMel and studied the correlation with etiological factors. We collected 47 primary ConjMel samples and performed next-generation sequencing of 400 genes. Hotspot mutations in BRAF, NRAS, HRAS, and KIT were observed in 16 (34%), 5 (11%), 2, and 2 cases, respectively. Patients with BRAF and CDKN2A-mutated ConjMel tended to be younger while the NF1-mutated one tended to be older. The eight tumors arising from nevi were enriched in CTNNB1 mutations (63% vs. 8%; Fisher's exact p-test = 0.001) compared to non-nevi ConjMel and five were devoid of BRAF, RAS, NF1, or KIT mutations, suggesting a specific oncogenic process in these tumors. The two KIT-mutated cases carried SF3B1 mutations and were located on sun-protected mucosa, a genotype shared with genital and anorectal mucosal melanomas. Targetable mutations were observed in ERBB2, IDH1, MET, and MAP2K1 (one occurrence each). Mutational landscape of ConjMel characterizes distinct molecular subtypes with oncogenic drivers common with mucosal and skin melanomas. CTNNB1 mutations were associated with nevus-derived ConjMel. Concomitant KIT/SF3B1 mutations in sun-protected cases suggest a common tumorigenic process with genital and anorectal mucosal melanomas.
CitationGardrat S, Houy A, Brooks K, Cassoux N, Barnhill R, Dayot S, et al. Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine. Cancers. 2021 Jul 30;13(15):3836.
- Recurrent KRAS, KIT and SF3B1 mutations in melanoma of the female genital tract.
- Authors: Cai YJ, Ke LF, Zhang WW, Lu JP, Chen YP
- Issue date: 2021 Jun 8
- Recurrent hotspot SF3B1 mutations at codon 625 in vulvovaginal mucosal melanoma identified in a study of 27 Australian mucosal melanomas.
- Authors: Quek C, Rawson RV, Ferguson PM, Shang P, Silva I, Saw RPM, Shannon K, Thompson JF, Hayward NK, Long GV, Mann GJ, Scolyer RA, Wilmott JS
- Issue date: 2019 Jan 29
- Melanoma with in-frame deletion of MAP2K1: a distinct molecular subtype of cutaneous melanoma mutually exclusive from BRAF, NRAS, and NF1 mutations.
- Authors: Williams EA, Montesion M, Shah N, Sharaf R, Pavlick DC, Sokol ES, Alexander B, Venstrom J, Elvin JA, Ross JS, Williams KJ, Tse JY, Mochel MC
- Issue date: 2020 Dec
- Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract.
- Authors: Tseng D, Kim J, Warrick A, Nelson D, Pukay M, Beadling C, Heinrich M, Selim MA, Corless CL, Nelson K
- Issue date: 2014 Aug
- GAB2 amplifications refine molecular classification of melanoma.
- Authors: Chernoff KA, Bordone L, Horst B, Simon K, Twadell W, Lee K, Cohen JA, Wang S, Silvers DN, Brunner G, Celebi JT
- Issue date: 2009 Jul 1