散发胰腺癌:BRCA2、ATM突变,不少见

JOURNAL OF CLINICAL ONCOLOGY

2017-08-02Report

24.008

影响因子

原标题:散发胰腺癌病人中的致病性基因突变

① 有害基因突变与散发性胰腺癌相关,且与家族性遗传有联系;② 为明确相关突变基因,该研究对854名胰腺导管腺癌,288名胰腺和壶腹周肿瘤,及51名胰腺切除手术患者的正常组织DNA进行测序,主要关注了胰腺癌易感基因在内的32个基因;③ 结果:854名胰腺癌患者中有33名有突变,而其中31名有BRCA2,ATM等突变,且患者要比没有突变的年轻;④ 没有明显家族性癌症发生史的患者也有相关种系突变基因,提示不能因没有家族史而忽略这些基因突变。

胰腺癌 基因突变 家族性遗传

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Title:
Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma

DOI:
10.1200/JCO.2017.72.3502

Abstract & Authors展开

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.

All Authors:
Koji Shindo,Jun Yu,Masaya Suenaga,Shahriar Fesharakizadeh,Christy Cho,Anne Macgregor-Das,Abdulrehman Siddiqui,P Dane Witmer,Koji Tamura,Tae Jun Song,Jose Alejandro Navarro Almario,Aaron Brant,Michael Borges,Madeline Ford,Thomas Barkley,Jin He,Matthew J Weiss,Christopher L Wolfgang,Nicholas J Roberts,Ralph H Hruban,Alison P Klein,Michael Goggins

First Authors:
Koji Shindo

Correspondence:
Michael Goggins

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