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Exomic Sequencing Identifies PALB2 As a Pancreatic Cancer Susceptibility Gene

Overview
Journal Science
Specialty Science
Date 2009 Mar 7
PMID 19264984
Citations 389
Authors
Sian Jones
Ralph H Hruban
Mihoko Kamiyama
Michael Borges
Xiaosong Zhang
D Williams Parsons
Jimmy Cheng-Ho Lin
Emily Palmisano
Kieran Brune
Elizabeth M Jaffee
Christine A Iacobuzio-Donahue
Anirban Maitra
Giovanni Parmigiani
Scott E Kern
Victor E Velculescu
Kenneth W Kinzler
Bert Vogelstein
James R Eshleman
Michael Goggins
Alison P Klein
Affiliations
Soon will be listed here.
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.

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References
1.
Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N . Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell. 2006; 22(6):719-729. DOI: 10.1016/j.molcel.2006.05.022. View
2.
Parsons D, Jones S, Zhang X, Cheng-Ho Lin J, Leary R, Angenendt P . An integrated genomic analysis of human glioblastoma multiforme. Science. 2008; 321(5897):1807-12. PMC: 2820389. DOI: 10.1126/science.1164382. View
3.
Turnbull C, Rahman N . Genetic predisposition to breast cancer: past, present, and future. Annu Rev Genomics Hum Genet. 2008; 9:321-45. DOI: 10.1146/annurev.genom.9.081307.164339. View
4.
Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A . PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet. 2007; 39(2):165-7. PMC: 2871593. DOI: 10.1038/ng1959. View
5.
McGuire A, Cho M, McGuire S, Caulfield T . Medicine. The future of personal genomics. Science. 2007; 317(5845):1687. PMC: 2220016. DOI: 10.1126/science.1147475. View