Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene.
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.
Jones
Siân
S
Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Baltimore, MD 21231, USA.
Hruban
Ralph H
RH
Kamiyama
Mihoko
M
Borges
Michael
M
Zhang
Xiaosong
X
Parsons
D Williams
DW
Lin
Jimmy Cheng-Ho
JC
Palmisano
Emily
E
Brune
Kieran
K
Jaffee
Elizabeth M
EM
Iacobuzio-Donahue
Christine A
CA
Maitra
Anirban
A
Parmigiani
Giovanni
G
Kern
Scott E
SE
Velculescu
Victor E
VE
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Eshleman
James R
JR
Goggins
Michael
M
Klein
Alison P
AP
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*
D018388:Codon, Terminator; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins