PT  - JOURNAL ARTICLE
AU  - Erin L. Young
AU  - Bryony A. Thompson
AU  - Deborah W. Neklason
AU  - Angela K. Snow
AU  - Matthew A. Firpo
AU  - Theresa Werner
AU  - Russell Bell
AU  - Nykole R. Sutherland
AU  - Ken R. Smith
AU  - Justin Berger
AU  - Alison Fraser
AU  - Amanda Gammon
AU  - Cathryn Koptiuch
AU  - Wendy K Kohlmann
AU  - Leigh Neumayer
AU  - David E. Goldgar
AU  - Sean J. Mulvihill
AU  - Lisa A. Cannon-Albright
AU  - Sean V. Tavtigian
TI  - Universal Panel Testing of Pancreatic Cancer Cases for Cancer Predisposition
AID  - 10.1101/195537
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 195537
4099  - http://biorxiv.org/content/early/2017/09/28/195537.short
4100  - http://biorxiv.org/content/early/2017/09/28/195537.full
AB  - Background and Aims Genes associated with hereditary breast and ovarian cancer (HBOC) and colorectal cancer (CRC) susceptibility have been shown to play a role in pancreatic cancer susceptibility. Germline genetic testing of pancreatic cancer cases could be beneficial for at-risk relatives with pathogenic variants in established HBOC and CRC genes, but it is unclear what proportion of pancreatic cancer cases harbor pathogenic variants in these genes.Methods 66 pancreatic cancer cases, unselected for family history and diagnosed at the Huntsman Cancer Hospital (HCH), were sequenced on a custom 34-gene panel including known HBOC and CRC genes. A second set of 156 unselected HCH pancreatic cancer cases were sequenced on an expanded 59-gene panel (n=95) or with a custom 14-gene clinical panel (n=61). Sequencing data from both sets of pancreatic cancer cases, the pancreatic cancer cases of the Cancer Genome Atlas (TCGA), and an unselected pancreatic cancer screen from the Mayo Clinic were combined in a meta-analysis to estimate the proportion of carriers with pathogenic and variants of uncertain significance.Results Approximately 8.9% of unselected pancreatic cancer cases at the HCH carried a variant with potential HBOC or CRC screening recommendations. A meta-analysis of unselected pancreatic cancer cases revealed that approximately 10.5% carry a pathogenic variant or HiP-VUS.Conclusion With the inclusion of both HBOC and CRC susceptibility genes in a panel test, unselected pancreatic cancer cases have a high enough percentage of carriers to rationalize genetic testing for identification of variants that could be further used in cascade testing of healthy relatives to increase HBOC and CRC surveillance measures.