title: CDKN2A germline mutations in familial pancreatic cancer.
abstract: OBJECTIVE
  To evaluate the prevalence of mutations in the CDKN2A gene encoding p16 and p14 in familial pancreatic cancer (FPC).
  
  
  BACKGROUND
  The genetic basis of FPC is still widely unknown. Recently, it has been shown that germline mutations in the p16 tumor suppressor gene can predispose to pancreatic cancer. The presence of p14 germline mutations has yet not been determined in this setting.
  
  
  METHODS
  Eighteen families with at least two first-degree relatives with histologically confirmed pancreatic cancer and five families with at least one patient with pancreatic cancer and another first-degree relative with malignant melanoma of the German National Case Collection for Familial Pancreatic Cancer were analyzed for CDKN2A germline mutations including p16 and p14 by direct DNA sequencing. All participating family members were genetically counseled and evaluated by a three-generation pedigree.
  
  
  RESULTS
  None of 18 FPC families without malignant melanoma revealed p16 mutations, compared to 2 of 5 families with pancreatic cancer and melanoma. Truncating p16 germline mutations Q50X and E119X were identified in the affected patients of pancreatic cancer plus melanoma families. None of the 23 families revealed p14 germline mutations.
  
  
  CONCLUSIONS
  CDKN2A germline mutations are rare in FPC families. However, these data provide further evidence for a pancreatic cancer-melanoma syndrome associated with CDKN2A germline mutations affecting p16. Thus, all members of families with combined occurrence of pancreatic cancer and melanoma should be counseled and offered screening for p16 mutations to identify high-risk family members who should be enrolled in a clinical screening program.
authors.affiliation: Department of Surgery, Institute of Biometrics and Medical Epidemiology, Philipps-University, Marburg, Germany. bartsch@mailer.uni-marburg.de
authors.forename: Detlef K
authors.initials: DK
authors.lastname: Bartsch
authors.forename: Mercedes
authors.initials: M
authors.lastname: Sina-Frey
authors.forename: Sven
authors.initials: S
authors.lastname: Lang
authors.forename: Anja
authors.initials: A
authors.lastname: Wild
authors.forename: Berthold
authors.initials: B
authors.lastname: Gerdes
authors.forename: Peter
authors.initials: P
authors.lastname: Barth
authors.forename: Ralf
authors.initials: R
authors.lastname: Kress
authors.forename: Robert
authors.initials: R
authors.lastname: Grützmann
authors.forename: Mario
authors.initials: M
authors.lastname: Colombo-Benkmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Hahn
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothmund
authors.forename: Harald
authors.initials: H
authors.lastname: Rieder
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D005858:Germany / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015995:Prevalence; D018570:Risk Assessment; D012494:Sampling Studies; D017678:Sex Distribution