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Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history

Authors :
John Kidd
Robert R. McWilliams
Anne Renee Hartman
Kari G. Chaffee
Gloria M. Petersen
Ann L. Oberg
Nanda Singh
Richard J. Wenstrup
Brian Allen
Neil Majithia
Source :
Genetics in medicine : official journal of the American College of Medical Genetics
Publication Year :
2016

Abstract

Background Panel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germline mutations. However, small sample sizes or number of genes evaluated limit prevalence estimates of these mutations. We estimated prevalence of mutations in PDAC patients with positive family history. Methods We sequenced 25 cancer susceptibility genes in lymphocyte DNA from 302 PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreatic Research Registry. Kindreds containing at least two first-degree relatives with PDAC met criteria for Familial Pancreatic Cancer (FPC), while the remaining were familial, but not FPC. Results Thirty-six patients (12%) carried at least one deleterious mutation in one of 11 genes. Of FPC patients, 25/185 (14%) were carriers, while 11/117 (9%) non-FPC patients with family history were carriers. Deleterious mutations (n) identified in PDAC patients were BRCA2 (11), ATM (8), CDKN2A (4), CHEK2 (4), MUTYH/MYH (3 heterozygotes, not biallelic), BRCA1 (2), and 1 each in BARD1, MSH2, NBN, PALB2, and PMS2. Novel mutations were found in ATM, BARD1, and PMS2. Conclusions Multiple susceptibility gene testing in PDAC patients with family history of pancreatic cancer is warranted regardless of FPC status, and will inform genetic risk counseling for families.

Details

ISSN :
15300366
Volume :
20
Issue :
1
Database :
OpenAIRE
Journal :
Genetics in medicine : official journal of the American College of Medical Genetics
Accession number :
edsair.doi.dedup.....f88f54369d0a65edd71956a74f236d9f