Mismatch repair (MMR) germline alterations are enriched among patients with uveal melanoma (UM), according to a study published online June 18 in JAMA Ophthalmology.
Anaïs Le Ven, from Inserm U1339 in Paris, and colleagues conducted a prospective cohort study involving 381 consecutive patients diagnosed with UM between July 2021 and February 2023 to identify new genetic alterations predisposing for UM. All participants consented to extended genetic testing; a panel of 122 genes predisposing to cancer were analyzed by targeted sequencing on germline DNA.
The researchers identified 79 pathogenic variants (PVs) in 70 participants. Twenty-one of these were found in clinically relevant genes, with an enrichment in the MMR genes involved in Lynch syndrome, suggesting that MMR germline PVs could predispose to UM.
One tumor from a participant carrying an MLH1 germline PV exhibited a monosomy 3, with loss of the wild-type allele of MLH1, which is located on chromosome 3. Loss of MLH1 expression was seen by immunohistochemistry; whole-genome sequencing of this tumor identified 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 author disclosed ties to the pharmaceutical industry; a second author holds related patents.
More information:
Anaïs Le Ven et al, Uveal Melanoma and the Lynch Syndrome Tumor Spectrum, JAMA Ophthalmology (2025). DOI: 10.1001/jamaophthalmol.2025.1779
© 2025 HealthDay. All rights reserved.
Citation:
Mismatch repair germline pathogenic variants could predispose to uveal melanoma (2025, June 21)
retrieved 21 June 2025
from https://medicalxpress.com/news/2025-06-mismatch-germline-pathogenic-variants-predispose.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
Mismatch repair (MMR) germline alterations are enriched among patients with uveal melanoma (UM), according to a study published online June 18 in JAMA Ophthalmology.
Anaïs Le Ven, from Inserm U1339 in Paris, and colleagues conducted a prospective cohort study involving 381 consecutive patients diagnosed with UM between July 2021 and February 2023 to identify new genetic alterations predisposing for UM. All participants consented to extended genetic testing; a panel of 122 genes predisposing to cancer were analyzed by targeted sequencing on germline DNA.
The researchers identified 79 pathogenic variants (PVs) in 70 participants. Twenty-one of these were found in clinically relevant genes, with an enrichment in the MMR genes involved in Lynch syndrome, suggesting that MMR germline PVs could predispose to UM.
One tumor from a participant carrying an MLH1 germline PV exhibited a monosomy 3, with loss of the wild-type allele of MLH1, which is located on chromosome 3. Loss of MLH1 expression was seen by immunohistochemistry; whole-genome sequencing of this tumor identified 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 author disclosed ties to the pharmaceutical industry; a second author holds related patents.
More information:
Anaïs Le Ven et al, Uveal Melanoma and the Lynch Syndrome Tumor Spectrum, JAMA Ophthalmology (2025). DOI: 10.1001/jamaophthalmol.2025.1779
© 2025 HealthDay. All rights reserved.
Citation:
Mismatch repair germline pathogenic variants could predispose to uveal melanoma (2025, June 21)
retrieved 21 June 2025
from https://medicalxpress.com/news/2025-06-mismatch-germline-pathogenic-variants-predispose.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
