PMS2 germline mutation c.943C>T (p.Arg315*)‐induced Lynch syndrome‐associated ovarian cancer

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation‐induced LS‐associated ovarian cancer (LSAOC) has rarely been reported. METHODS: Next‐generation sequencing (NGS) or Sanger sequencing was used to detect the genetic status of one family including four generations with 16 members. Then, quantitative real‐time PCR (qPCR), western blotting, immunohistochemistry (IHC) staining, and Swiss‐Model software were used to identify the function of the PMS2 mutation. RESULTS: Five individuals [I‐1, II‐1, II‐2, II‐4, and III‐2 (proband)] suffered from LS‐associated cancers, for example, colon cancer, gastric cancer, and ovarian cancer, with the age of onset ranging from 39 to 70 years old. A PMS2 germline heterozygous mutation (c.943C>T) was confirmed in three members [II‐9, III‐2, and IV‐1] by gene sequencing. In addition, this PMS2 mutation was verified by qPCR, western blotting, and IHC, and a dramatic change with partial loss of the C‐terminal domain in an α‐helix might be exhibited. CONCLUSION: Carrying PMS2 germline mutations (c.943C>T) confers an extremely high susceptibility of suffering from LS‐associated cancers. Thus, close clinical monitoring and prophylactic surgery is highly recommended to help reduce the morbidity and mortality of LS‐associated cancers.