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Updated: May 29, 2026

Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Pancreatic cancer and a novel MSH2 germline alteration
Noralane M Lindor1, Gloria M Petersen, Amanda B Spurdle
1Department of Medical Genetics and †Department of Health Science Research, Mayo Clinic, Rochester, MN 55905, USA. nlindor@mayo.edu
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.
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