Article

Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene.

Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Baltimore, MD 21231, USA.
Science (impact factor: 31.2). 04/2009; 324(5924):217. DOI:10.1126/science.1171202
Source: PubMed

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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Keywords

96 additional patients
 
appeared responsible
 
binding partner
 
complete
 
complete sequencing
 
distinct protein-truncating mutations
 
familial breast cancer
 
familial pancreatic cancer
 
gene responsible
 
hereditary disease
 
PALB2
 
PALB2 mutations
 
PALB2 protein
 
pancreatic cancer
 
patient's predisposition
 
protein-coding genes
 
susceptibility gene
 
truncating mutation