1. <scp>MLH1</scp> epimutation is a rare mechanism for Lynch syndrome: A case report and review of the literature
- Author
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Miralem Mrkonjic, Melyssa Aronson, Lea Velsher, Gulisa Turashvili, Tracy Graham, and Roman E. Zyla
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,Vulvar Squamous Cell Carcinoma ,Genetic counseling ,Biology ,MLH1 ,Germline ,Epigenesis, Genetic ,Sebaceous adenoma ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Genetics ,medicine ,Humans ,Promoter Regions, Genetic ,neoplasms ,Germ-Line Mutation ,Endometrial cancer ,nutritional and metabolic diseases ,DNA Methylation ,Middle Aged ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,digestive system diseases ,Lynch syndrome ,030220 oncology & carcinogenesis ,Cancer research ,Female ,MutL Protein Homolog 1 - Abstract
Endometrial carcinoma is one of the prototypical malignancies associated with Lynch syndrome, an inherited cancer syndrome most commonly caused by germline mutations in DNA mismatch repair (MMR) genes, although rare alternative mechanisms also exist. In this report, we describe a patient first diagnosed with colorectal cancer at age 33, then vulvar squamous cell carcinoma, facial sebaceous adenoma/sebaceoma, and finally endometrial carcinoma at age 52. All tumors were MLH1/PMS2-deficient by immunohistochemistry, and MLH1 promoter methylation was identified in the endometrial cancer. Germline MLH1 testing was negative for pathogenic variants, but she was subsequently diagnosed with Lynch syndrome secondary to a germline monoallelic constitutional epimutation of the MLH1 promoter. Identification of patients displaying a Lynch syndrome phenotype but lacking germline MMR mutations is important to avoid delays in the diagnosis of Lynch syndrome as well as the initiation of appropriate cancer screening and genetic counseling.
- Published
- 2021