RT Journal Article
SR Electronic
T1 Universal Panel Testing of Pancreatic Cancer Cases for Cancer Predisposition
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 195537
DO 10.1101/195537
A1 Erin L. Young
A1 Bryony A. Thompson
A1 Deborah W. Neklason
A1 Angela K. Snow
A1 Matthew A. Firpo
A1 Theresa Werner
A1 Russell Bell
A1 Nykole R. Sutherland
A1 Ken R. Smith
A1 Justin Berger
A1 Alison Fraser
A1 Amanda Gammon
A1 Cathryn Koptiuch
A1 Wendy K Kohlmann
A1 Leigh Neumayer
A1 David E. Goldgar
A1 Sean J. Mulvihill
A1 Lisa A. Cannon-Albright
A1 Sean V. Tavtigian
YR 2017
UL http://biorxiv.org/content/early/2017/09/28/195537.abstract
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.