title: Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene.
abstract: Through complete sequencing of the protein-coding genes in a patient with familial pancreatic cancer, we identified a germline, truncating mutation in PALB2 that appeared responsible for this patient's predisposition to the disease. Analysis of 96 additional patients with familial pancreatic cancer revealed three distinct protein-truncating mutations, thereby validating the role of PALB2 as a susceptibility gene for pancreatic cancer. PALB2 mutations have been previously reported in patients with familial breast cancer, and the PALB2 protein is a binding partner for BRCA2. These results illustrate that complete, unbiased sequencing of protein-coding genes can lead to the identification of a gene responsible for a hereditary disease.
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Baltimore, MD 21231, USA.
authors.forename: Siân
authors.initials: S
authors.lastname: Jones
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kamiyama
authors.forename: Michael
authors.initials: M
authors.lastname: Borges
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Zhang
authors.forename: D Williams
authors.initials: DW
authors.lastname: Parsons
authors.forename: Jimmy Cheng-Ho
authors.initials: JC
authors.lastname: Lin
authors.forename: Emily
authors.initials: E
authors.lastname: Palmisano
authors.forename: Kieran
authors.initials: K
authors.lastname: Brune
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Jaffee
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kern
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
authors.forename: Alison P
authors.initials: AP
authors.lastname: Klein
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D018388:Codon, Terminator; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018388:Codon, Terminator; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins