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 6 SD, 60.8 6 10.6 v 65.1 6 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3382-3390 |
| Number of pages | 9 |
| Journal | Journal of Clinical Oncology |
| Volume | 35 |
| Issue number | 30 |
| DOIs | |
| State | Published - Oct 20 2017 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. / Shindo, Koji; Yu, Jun; Suenaga, Masaya; Fesharakizadeh, Shahriar; Cho, Christy; Macgregor-Das, Anne; Siddiqui, Abdulrehman; Witmer, P. Dane; Tamura, Koji; Song, Tae Jun; Almario, Jose Alejandro Navarro; Brant, Aaron; Borges, Michael; Ford, Madeline; Barkley, Thomas; He, Jin; Weiss, Matthew J; Wolfgang, Christopher; Roberts, Nicholas; Hruban, Ralph H; Klein, Alison; Goggins, Michael S.
In: Journal of Clinical Oncology, Vol. 35, No. 30, 20.10.2017, p. 3382-3390.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma
AU - Shindo, Koji
AU - Yu, Jun
AU - Suenaga, Masaya
AU - Fesharakizadeh, Shahriar
AU - Cho, Christy
AU - Macgregor-Das, Anne
AU - Siddiqui, Abdulrehman
AU - Witmer, P. Dane
AU - Tamura, Koji
AU - Song, Tae Jun
AU - Almario, Jose Alejandro Navarro
AU - Brant, Aaron
AU - Borges, Michael
AU - Ford, Madeline
AU - Barkley, Thomas
AU - He, Jin
AU - Weiss, Matthew J
AU - Wolfgang, Christopher
AU - Roberts, Nicholas
AU - Hruban, Ralph H
AU - Klein, Alison
AU - Goggins, Michael S
PY - 2017/10/20
Y1 - 2017/10/20
N2 - 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 6 SD, 60.8 6 10.6 v 65.1 6 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.
AB - 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 6 SD, 60.8 6 10.6 v 65.1 6 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.
UR - http://www.scopus.com/inward/record.url?scp=85028970364&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028970364&partnerID=8YFLogxK
U2 - 10.1200/JCO.2017.72.3502
DO - 10.1200/JCO.2017.72.3502
M3 - Article
C2 - 28767289
AN - SCOPUS:85028970364
VL - 35
SP - 3382
EP - 3390
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 30
ER -