To describe a novel MSH2 missense alteration co-segregating with pancreatic cancer.
Observational study of a kindred in which a novel MSH2 missense alteration was identified.
We report a family in which a MSH2 P349L missense alteration is co-segregating with pancreatic cancers among three 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 interpretation of this DNA alteration as likely pathogenic.
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.
Keywords: pancreatic cancer, HNPCC, Lynch Syndrome, hereditary, genetics