Mismatch restore (MMR) germline alterations are enriched amongst sufferers with uveal melanoma (UM), in accordance with a examine revealed on-line June 18 in JAMA Ophthalmology.
Anaïs Le Ven, from Inserm U1339 in Paris, and colleagues carried out a potential cohort examine involving 381 consecutive sufferers identified with UM between July 2021 and February 2023 to determine new genetic alterations predisposing for UM. All members consented to prolonged genetic testing; a panel of 122 genes predisposing to most cancers had been analyzed by focused sequencing on germline DNA.
The researchers recognized 79 pathogenic variants (PVs) in 70 members. Twenty-one of those had been present in clinically related genes, with an enrichment within the MMR genes concerned in Lynch syndrome, suggesting that MMR germline PVs might predispose to UM.
One tumor from a participant carrying an MLH1 germline PV exhibited a monosomy 3, with lack of the wild-type allele of MLH1, which is positioned on chromosome 3. Lack of MLH1 expression was seen by immunohistochemistry; whole-genome sequencing of this tumor recognized MMR variant signatures SBS6, ID1, and ID2.
“These findings suggest that MMR germline alterations could explain at least a portion of UM genetics, and that UM could be part of the Lynch syndrome spectrum,” the authors write.
One creator disclosed ties to the pharmaceutical business; a second creator holds associated patents.
Extra info:
Anaïs Le Ven et al, Uveal Melanoma and the Lynch Syndrome Tumor Spectrum, JAMA Ophthalmology (2025). DOI: 10.1001/jamaophthalmol.2025.1779
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