Prevalence of Pathogenic Mutations in Cancer Predisposition Genes among Pancreatic Cancer Patients.
The prevalence of germline pathogenic mutations in a comprehensive panel of cancer predisposition genes is not well-defined for patients with pancreatic ductal adenocarcinoma (PDAC). To estimate the frequency of mutations in a panel of 22 cancer predisposition genes, 96 patients unselected for a family history of cancer who were recruited to the Mayo Clinic Pancreatic Cancer patient registry over a 12-month period were screened by next-generation sequencing. Fourteen pathogenic mutations in 13 patients (13.5%) were identified in eight genes: four in ATM, two in BRCA2, CHEK2, and MSH6, and one in BARD1, BRCA1, FANCM, and NBN. These included nine mutations (9.4%) in established pancreatic cancer genes. Three mutations were found in patients with a first-degree relative with PDAC, and 10 mutations were found in patients with first- or second-degree relatives with breast, pancreas, colorectal, ovarian, or endometrial cancers. These results suggest that a substantial proportion of patients with PDAC carry germline mutations in predisposition genes associated with other cancers and that a better understanding of pancreatic cancer risk will depend on evaluation of families with broad constellations of tumors. These findings highlight the need for recommendations governing germline gene-panel testing of patients with pancreatic cancer.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Chunling
C
Hu
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Steven N
SN
Hart
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
William R
WR
Bamlet
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Raymond M
RM
Moore
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Kannabiran
K
Nandakumar
Medical Genome Facility, Mayo Clinic, Rochester, Minnesota.
Bruce W
BW
Eckloff
Medical Genome Facility, Mayo Clinic, Rochester, Minnesota.
Yean K
YK
Lee
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Gloria M
GM
Petersen
Department of Oncology, Mayo Clinic, Rochester, Minnesota.
Robert R
RR
McWilliams
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. couch.fergus@mayo.edu.
Fergus J
FJ
Couch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies
D014408:Biomarkers, Tumor