Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history.
Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history.
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DOI：
10.1038/gim.2017.85
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Petersen GM
中科院分区：
文献类型：
--
作者：
Chaffee KG;Oberg AL;McWilliams RR;Majithia N;Allen BA;Kidd J;Singh N;Hartman AR;Wenstrup RJ;Petersen GM
基于小组的基因检测已经确定了越来越多携带生殖系突变的胰腺导管腺癌（PDAC）患者。然而，小样本量或评估的基因数量限制了这些突变的患病率估计。我们估计了具有阳性家族史的PDAC患者的突变患病率。我们对来自马约诊所胰腺研究登记处生物样本资源的302名PDAC患者的淋巴细胞DNA中的25个癌症易感基因进行了测序。至少有两个一级亲属患有PDAC的亲属符合家族性胰腺癌（FPC）的标准，而其余的是家族性的，但不是FPC。36名患者（12%）在11个基因中的一个中携带至少一个有害突变。在FPC患者中，25/185（14%）为携带者，而11/117（9%）有家族史的非FPC患者为携带者。PDAC患者中发现的有害突变（n）为BRCA 2（11）、ATM（8）、CDKN 2A（4）、CHEK 2（4）、MUTYH/MYH（3个杂合子，非双等位基因）、BRCA 1（2），BARD 1、MSH 2、NBN、PALB 2和PMS 2各1个。在ATM、BARD 1和PMS 2中发现了新的突变。无论FPC状态如何，有胰腺癌家族史的PDAC患者的多易感基因检测都是必要的，并将为家庭提供遗传风险咨询。
Panel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germline 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. We 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. Thirty-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. Multiple 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.
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影响因子：
29.4
作者：
Grant RC;Selander I;Connor AA;Selvarajah S;Borgida A;Briollais L;Petersen GM;Lerner-Ellis J;Holter S;Gallinger S
通讯作者：
Gallinger S
影响因子：
4.5
作者：
Rosenthal, Eric T.;Evans, Brent;Manley, Susan
通讯作者：
Manley, Susan
影响因子：
3.5
作者：
Barnetson, Rebecca A.;Devlin, L.;Porteous, M. E.
通讯作者：
Porteous, M. E.
影响因子：
64.8
作者：
GATTI, RA;BERKEL, I;YODER, F
通讯作者：
YODER, F
DOI：
10.1158/1055-9965.epi-15-0455
发表时间：
2016-01
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Hu C;Hart SN;Bamlet WR;Moore RM;Nandakumar K;Eckloff BW;Lee YK;Petersen GM;McWilliams RR;Couch FJ
通讯作者：
Couch FJ