Objective: The objective of this study was to describe a novel MSH2 missense alteration cosegregating with pancreatic cancer. Methods: The method used was an observational study of a kindred in which a novel MSH2 missense alteration was identified. Results: We report a family in which a MSH2 P349L missense alteration is cosegregating with pancreatic cancers among 3 nonsmoking first-degree relatives. Lynch syndrome-related tumors from individuals carrying this alteration consistently showed loss of immunohistochemical expression of MSH2, and in silico analyses support the interpretation of this DNA alteration as likely pathogenic. Conclusions: The MSH2 P349L may increase the risk for pancreatic cancer beyond the usual mutations in DNA mismatch repair genes; however, studies of additional families with the identical missense alteration are needed to confirm this initial impression.
- Lynch syndrome
- hereditary nonpolyposis colorectal cancer
- pancreatic cancer
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism