Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene

S Jones, RH Hruban, M Kamiyama, M Borges, X Zhang… - Science, 2009 - science.org
S Jones, RH Hruban, M Kamiyama, M Borges, X Zhang, DW Parsons, JCH Lin, E Palmisano…
Science, 2009science.org
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 …
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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