title: Pancreatic cancer and a novel MSH2 germline alteration.
abstract: 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.
authors.affiliation: Department of Medical Genetics and †Department of Health Science Research, Mayo Clinic, Rochester, MN 55905, USA. nlindor@mayo.edu
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: Bryony
authors.initials: B
authors.lastname: Thompson
authors.forename: David E
authors.initials: DE
authors.lastname: Goldgar
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D040941:Heredity; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D020125:Mutation, Missense; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype
chemical_list: C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein