Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene

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.

Fig. 1

Location of mutations in the PALB2 gene. Exons are represented as blue boxes and introns as black lines (not to scale). Mutations previously identified in patients with familial breast cancer or Fanconi Anemia are shown in black or purple, respectively. Germline mutations identified in patients with familial pancreatic cancer are shown above the gene in red.