PREVALENCE OF MISMATCH REPAIR GENE MUTATIONS IN UVEAL MELANOMA.

Autor:	Toomey CB; Departments of Ophthalmology, and.; Pathology, UC San Diego, La Jolla, California., Protopsaltis NJ; School of Medicine, UC San Diego, La Jolla, California., Phou S; Pathology, UC San Diego, La Jolla, California., Bakhoum MF; Departments of Ophthalmology, and., Thorson JA; Pathology, UC San Diego, La Jolla, California., Ediriwickrema LS; Departments of Ophthalmology, and., Korn BS; Departments of Ophthalmology, and., Kikkawa DO; Departments of Ophthalmology, and., Goldbaum MH; Departments of Ophthalmology, and., Lin JH; Departments of Ophthalmology, and.; Pathology, UC San Diego, La Jolla, California.; VA San Diego Healthcare System, San Diego, California.; Departments of Ophthalmology and Pathology, Stanford University School of Medicine, Stanford, California; and.; VA Palo Alto Healthcare System, Palo Alto, California.
Jazyk:	angličtina
Zdroj:	Retina (Philadelphia, Pa.) [Retina] 2020 Nov; Vol. 40 (11), pp. 2216-2220.
DOI:	10.1097/IAE.0000000000002732
Abstrakt:	Purpose: Uveal melanomas are associated with characteristic genetic changes. Germline mutations in mismatch repair (MMR) genes and microsatellite instability have been implicated in the development of numerous malignant neoplasms such as colon and ovarian cancers. The frequency of MMR defects in uveal melanomas has yet to be determined. Methods: Here, we analyzed the frequency of MMR gene mutations in uveal melanoma specimens from the University of California, San Diego (UCSD), The Cancer Genome Atlas (TGCA), and the Catalogue of Somatic Mutations in Cancer (COSMIC). Results: We identified only two mutations in a MMR gene: one premature stop codon in the PMS gene within the UCSD cohort (0.5% frequency) and one in-frame deletion in MSH3 within the COSMIC database (0.8% frequency). We report copy number variation of MLH1 in monosomy 3 and show decreased mRNA expression of MLH1 in uveal melanoma specimens with monosomy 3. Expression levels of MLH1 were not found to correlate with the observed number of total mutations. Conclusion: Overall, we show that mutations in MMR genes in uveal melanoma specimens are exceedingly rare, and although one copy of MLH1 is lost in monosomy 3, it does not seem to have pathologic consequences in uveal melanoma pathogenesis.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu