Mismatch repair germline pathogenic variants could predispose to uveal melanoma

Mismatch restore (MMR) germline alterations are enriched amongst sufferers with uveal melanoma (UM), based on a research printed on-line June 18 in JAMA Ophthalmology.

Anaïs Le Ven, from Inserm U1339 in Paris, and colleagues carried out a potential cohort research involving 381 consecutive sufferers recognized 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 have been analyzed by focused sequencing on germline DNA.

The researchers recognized 79 pathogenic variants (PVs) in 70 members. Twenty-one of those have 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 situated 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 counsel that MMR germline alterations might clarify a minimum of a portion of UM genetics, and that UM could possibly be a part of the Lynch syndrome spectrum,” the authors write.

One writer disclosed ties to the pharmaceutical trade; a second writer holds associated patents.

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