title: Germ line Fanconi anemia complementation group C mutations and pancreatic cancer.
abstract: Biallelic mutations in Fanconi anemia complementation group genes disrupt DNA repair and result in the complex Fanconi anemia phenotype. In addition, germ line mutations in the BRCA2/FANCD1 Fanconi anemia complementation group gene have also been implicated in predisposition to a number of cancers including pancreatic cancer. The recent identification of FANCC and FANCG mutations in resected pancreatic tumors selected for loss of heterozygosity on chromosome 9, some of which were present in the germ line DNA, suggests that inactivation of these and other Fanconi complementation group genes may contribute to pancreatic cancer. To further assess the relevance of FANCC and FANCG mutations to pancreatic cancer we conducted a mutation screen of these genes in DNA from blood of 421 sequentially collected pancreatic cancer cases diagnosed at the Mayo Clinic. Two truncating FANCC mutations but no truncating FANCG mutations were identified in young onset (<55 years) pancreatic cancer cases with no family history of pancreatic cancer. Both mutations were associated with loss of heterozygosity of the wild-type allele in corresponding pancreatic tumors. In addition, no truncating mutations were identified in germ line DNA from blood of 658 control individuals undergoing routine colonoscopy. Taken together these data support the assertion that inherited mutations in FANCC can predispose to pancreatic cancer.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. Couch.Fergus@mayo.edu
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: Michele R
authors.initials: MR
authors.lastname: Johnson
authors.forename: Kari
authors.initials: K
authors.lastname: Rabe
authors.forename: Lisa
authors.initials: L
authors.lastname: Boardman
authors.forename: Robert
authors.initials: R
authors.lastname: McWilliams
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Gloria
authors.initials: G
authors.lastname: Petersen
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000235:genetics; D002291:Carcinoma, Papillary / Q000097:blood / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; C499909:FANCG protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins