open access: Evidence of constitutional MLH1 epimutation associated to transgenerational inheritance of cancer susceptibility - Human Mutation

Blogger's Note: see references in paper to ovarian cancer; BRAF mutations


Epimutation , epimutation meaning , definition of epimutation , what is epimutation - A heritable change in gene expression that does not affect the actual base pair sequence of DNA . The first sign of cellular abnormality in some tumors is an epimutation—a change in heritable chromatin marks , such as an increase or decrease in the density of DNA methylation.
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"In addition, two patients were included in the study because of personal medical past history (endometrial cancer at the age of 24, and multiple sebaceous tumors associated with ovary cancer at the age of 44, respectively) strongly suggesting Lynch syndrome. The mean age of patients at diagnosis of the first Lynch syndrome-related cancer was 46 years (range, 24–74)."

"In conclusion, we have shown that constitutional epimutations in MMR genes constitute a rare cause of Lynch syndrome. However, they are associated to a real risk of transgenerational inheritance of cancer susceptibility. Moreover, tumors from patients with constitutional MLH1 epimutation can display BRAF mutations, mimicking MSI-H sporadic tumors. Altogether, these findings may have important implications for future diagnostic strategies and genetic counseling."