TY - JOUR
T1 - Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history
AU - Chaffee, Kari G.
AU - Oberg, Ann L.
AU - McWilliams, Robert R.
AU - Majithia, Neil
AU - Allen, Brian A.
AU - Kidd, John
AU - Singh, Nanda
AU - Hartman, Anne Renee
AU - Wenstrup, Richard J.
AU - Petersen, Gloria M.
N1 - Publisher Copyright:
© American College of Medical Genetics and Genomics.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - PurposePanel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germ-line 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.MethodsWe 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.ResultsThirty-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.ConclusionMultiple 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.
AB - PurposePanel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germ-line 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.MethodsWe 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.ResultsThirty-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.ConclusionMultiple 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.
KW - familial pancreatic cancer (FPC)
KW - pancreatic ductal adenocarcinoma (PDAC)
KW - pathogenic variant (PV)
KW - variant of uncertain significance (VUS)
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U2 - 10.1038/gim.2017.85
DO - 10.1038/gim.2017.85
M3 - Article
C2 - 28726808
AN - SCOPUS:85040450236
SN - 1098-3600
VL - 20
SP - 119
EP - 127
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 1
ER -