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Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma
- Source :
- Journal of Clinical Oncology. 35:3382-3390
- Publication Year :
- 2017
- Publisher :
- American Society of Clinical Oncology (ASCO), 2017.
-
Abstract
- Purpose Deleterious germline mutations contribute to pancreatic cancer susceptibility and are well documented in families in which multiple members have had pancreatic cancer. Methods To define the prevalence of these germline mutations in patients with apparently sporadic pancreatic cancer, we sequenced 32 genes, including known pancreatic cancer susceptibility genes, in DNA prepared from normal tissue obtained from 854 patients with pancreatic ductal adenocarcinoma, 288 patients with other pancreatic and periampullary neoplasms, and 51 patients with non-neoplastic diseases who underwent pancreatic resection at Johns Hopkins Hospital between 2000 and 2015. Results Thirty-three (3.9%; 95% CI, 3.0% to 5.8%) of 854 patients with pancreatic cancer had a deleterious germline mutation, 31 (3.5%) of which affected known familial pancreatic cancer susceptibility genes: BRCA2 (12 patients), ATM (10 patients), BRCA1 (3 patients), PALB2 (2 patients), MLH1 (2 patients), CDKN2A (1 patient), and TP53 (1 patient). Patients with these germline mutations were younger than those without (mean ± SD, 60.8 ± 10.6 v 65.1 ± 10.5 years; P = .03). Deleterious germline mutations were also found in BUB1B (1) and BUB3 (1). Only three of these 33 patients had reported a family history of pancreatic cancer, and most did not have a cancer family history to suggest an inherited cancer syndrome. Five (1.7%) of 288 patients with other periampullary neoplasms also had a deleterious germline mutation. Conclusion Germline mutations in pancreatic cancer susceptibility genes are commonly identified in patients with pancreatic cancer without a significant family history of cancer. These deleterious pancreatic cancer susceptibility gene mutations, some of which are therapeutically targetable, will be missed if current family history guidelines are the main criteria used to determine the appropriateness of gene testing.
- Subjects :
- Adult
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
PALB2
MLH1
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Germline mutation
Gene Frequency
CDKN2A
Pancreatic cancer
Internal medicine
Prevalence
medicine
Carcinoma
Humans
Genetic Predisposition to Disease
Germ-Line Mutation
Aged
Aged, 80 and over
business.industry
Deleterious Germline Mutation
Sequence Analysis, DNA
Middle Aged
medicine.disease
United States
Pancreatic Neoplasms
030104 developmental biology
030220 oncology & carcinogenesis
Adenocarcinoma
Female
business
Carcinoma, Pancreatic Ductal
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....d95258df5adfd8370ceeb98e71ab44cc