Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene

• Published in: Science (American Association for the Advancement of Science) Vol. 324; no. 5924; p. 217
• Main Authors: Jones, Siân, Hruban, Ralph H, Kamiyama, Mihoko, Borges, Michael, Zhang, Xiaosong, Parsons, D. Williams, Lin, Jimmy Cheng-Ho, Palmisano, Emily, Brune, Kieran, Jaffee, Elizabeth M, Iacobuzio-Donahue, Christine A, Maitra, Anirban, Parmigiani, Giovanni, Kern, Scott E, Velculescu, Victor E, Kinzler, Kenneth W, Vogelstein, Bert, Eshleman, James R, Goggins, Michael, Klein, Alison P
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 10.04.2009; The American Association for the Advancement of Science
• Subjects: Alleles; Binding sites; Biological and medical sciences; Breast Neoplasms - genetics; Brevia; Cancer; Codon, Terminator; Electronic publishing; Exons; Fanconi Anemia Complementation Group N Protein; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genetic markers; Genetic mutation; Genetic Predisposition to Disease; Germ cells; Germ-Line Mutation; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Mutation; Nuclear Proteins - genetics; Pancreatic cancer; Pancreatic neoplasms; Pancreatic Neoplasms - genetics; Pedigree; Proteins; Research facilities; Sequence Analysis, DNA; Sequence Deletion; Sequencing; Stop codon; Tumor Suppressor Proteins - genetics; Tumors; Human; Cancerology; Gene; Pancreas cancer; Predisposition; Genetics; Digestive diseases; Familial cancer; Malignant tumor; Sequencing; Cancer; Pancreatic disease
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1171202

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.