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This article is part of the supplement: Beyond the Genome: The true gene count, human evolution and disease genomics

Open Badges Invited speaker presentation

Gene discovery for complex diseases using exomic sequencing: identifying pancreatic cancer susceptibility genes

Alison P Klein

  • Correspondence: Alison P Klein

Author Affiliations

Departments of Oncology, Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA

Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, MD 21231, USA

Genome Biology 2010, 11(Suppl 1):I4  doi:10.1186/gb-2010-11-s1-i4

The electronic version of this article is the complete one and can be found online at:

Published:11 October 2010

© 2010 Klein; licensee BioMed Central Ltd.

Invited speaker presentation

Traditional methods of gene discovery, candidate gene and linkage approaches, have yielded very few pancreatic cancer susceptibility loci, such that genetic basis of ~90% of the familial clustering of pancreatic cancer is unknown. The recent advances and cost reductions in genome sequencing have enabled us to identify pancreatic cancer susceptibility genes through exomic sequencing patients with a family history of pancreatic cancer. Individuals that have an inherited tumor suppressor gene often lose the wild- type allele through loss of heterozygosity or somatic mutation. Therefore, we examined a patient's tumor and germ-line DNA for genes with evidence of both inherited and somatic variants that were likely to result in the absence of a functional protein in the patient's tumor. We also analyzed data on normal genetic variation in published databases and in individuals without pancreatic cancer. These analyses identified PALB2 as candidate pancreatic cancer gene. The role of PALB2 in familial pancreatic cancer was validated by studying an additional 96 pancreatic cancer patients. Large-scale follow-up studies of over 500 familial pancreatic cancer patients are currently underway.