Uveal Melanoma & Mismatch Repair Genes: Risk Factors
- Genetic alterations in mismatch repair (MMR) genes may predispose individuals to uveal melanoma (UM), a new study indicates.
- Researchers, led by Anaïs Le Ven from Inserm U1339 in Paris, conducted a prospective cohort study involving 381 UM patients diagnosed between July 2021 and February 2023.
- The analysis revealed 79 pathogenic variants in 70 participants.
New research reveals a critically important link: alterations in mismatch repair (MMR) genes may heighten the risk of uveal melanoma (UM). The study, published in *JAMA Ophthalmology*, underscores the role that specific genes, particularly MMR genes, play in UM development, suggesting a possible connection to Lynch syndrome.Scientists identified pathogenic variants in MMR genes, solidifying the part genetics takes in this aggressive cancer. This piece, highlighted on News Directory 3, explores the implications of genetic screening for those with a family history.Delve into the intricacies of this study and discover what’s next in the fight against UM.
DNA Repair Genes Play a Role in Uveal Melanoma Risk
Updated June 21, 2025
Genetic alterations in mismatch repair (MMR) genes may predispose individuals to uveal melanoma (UM), a new study indicates. The research, published in JAMA Ophthalmology, suggests a potential link between UM and Lynch syndrome.
Researchers, led by Anaïs Le Ven from Inserm U1339 in Paris, conducted a prospective cohort study involving 381 UM patients diagnosed between July 2021 and February 2023. The study aimed to identify genetic factors that could predispose individuals to UM. All participants underwent genetic testing, with 122 cancer-related genes analyzed via targeted sequencing of germline DNA.
The analysis revealed 79 pathogenic variants in 70 participants. Of these, 21 were located in clinically relevant genes, with a notable enrichment in MMR genes associated with Lynch syndrome. This finding suggests that germline pathogenic variants in MMR genes could increase susceptibility to UM. The study highlights the significant role that genetics play in cancer development, and the part that specific genes have in tumor growth.
Further analysis of a tumor from a participant with an MLH1 germline pathogenic variant showed monosomy 3, along with loss of the wild-type allele of MLH1. Immunohistochemistry confirmed the loss of MLH1 expression.Whole-genome sequencing identified MMR variant signatures SBS6,ID1,and ID2 in this tumor.
“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 wrote.
What’s next
The study’s findings could lead to improved genetic screening and risk assessment for individuals with a family history of UM or Lynch syndrome. Further research is needed to fully understand the mechanisms by which MMR gene alterations contribute to UM development.