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Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene
- 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.
- Science 2009 v.324 no.5924 pp. 217
- breast neoplasms, genes, genetic disorders, germ cells, mutation, pancreatic neoplasms, patients, tumor suppressor proteins
- 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.