Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene
By Siân Jones, R. Hruban, Mihoko Kamiyama, Michael Borges, Xiaosong Zhang, D. W. Parsons, Jimmy Lin, Emily Palmisano, K. Brune, E. Jaffee and 10 more. Science, 2009
806 citations recorded by the source corpus.
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.
Subfields: Cancer Research, Genetics, Oncology
View Paper: https://www.semanticscholar.org/paper/6301c5f25d37aa2ba956cf71170ec123c6005570
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
In Genetics
In Oncology
Citations in the corpus
- Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. (2015, neutral): “P13 (Italian) 4 LBC (39) GC (53), GC (44), BC and uterine (34), BC (NA) Brain (NA) DD SDHB (1) c.”
- Epidemiology of pancreatic cancer: an overview (2009, background): “The partner and localizer of BRCA2 ( PALB2 ) gene, which is associated with Fanconi anemia and breast cancer predisposition, has also been identified as a candidate pancreatic cancer susceptibility gene”
- Homologous recombination and human health: the roles of BRCA1, BRCA2 and associated proteins (2015, background): “Monoallelic PALB2 mutations have also been associated with pancreatic and ovarian cancer susceptibility (Jones et al. 2009; Walsh et al. 2011).”
- Targeted Capture and Massively Parallel Sequencing of Twelve Human Exomes (2009, neutral): “…was overcome recently in the context of hereditary pancreatic cancer by restricting focus only to nonsense mutations and also resequencing tumour DNA from the same individual, but this approach greatly limits sensitivity and is only relevant to a subset of mechanisms within one disease class 28 .”
- Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination (2010, positive): “Recently, PALB2 has also been linked to pancreatic cancer susceptibility, being the second most frequently mutated gene in affected people, after BRCA2 (ref”
- Advances in understanding cancer genomes through second-generation sequencing (2010, background): “and of germline mutations in the gene encoding partner and localizer of BRCA2 ( PALB2 ) in patients with pancreatic carcinom”
- Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene (2010, background): “In addition, the high penetrance of mutations impairing RAD51C function, and the causative link with the occurrence of gynecological cancers, justifies testing of other malignancie”
- Recent progress in pancreatic cancer (2013, methodology): “PALB2 in familial pancreatic cancer kindreds was made by Jones et al using a whole-exome sequencing approach.(30) Subsequent studies have replicated this finding.”