Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene

  • Science. 2009 Apr 10;324(5924):217. doi: 10.1126/science.1171202.
Siân Jones  1 ,  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
  • 1. Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Baltimore, MD 21231, USA.
PMID: 19264984 DOI: 10.1126/science.1171202
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.