Prevalence of Pathogenic Mutations in Cancer Predisposition Genes among Pancreatic Cancer Patients.
Prevalence of Pathogenic Mutations in Cancer Predisposition Genes among Pancreatic Cancer Patients.
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DOI：
10.1158/1055-9965.epi-15-0455
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Couch FJ
中科院分区：
文献类型：
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作者：
Hu C;Hart SN;Bamlet WR;Moore RM;Nandakumar K;Eckloff BW;Lee YK;Petersen GM;McWilliams RR;Couch FJ
在胰腺导管腺癌（PDAC）患者中，一组全面的癌症易感基因中生殖系致病性突变的患病率尚未明确。为了估计一组22个癌症易感基因的突变频率，通过下一代测序筛选了96名有癌症家族史的患者，这些患者在12个月内被招募到马约诊所胰腺癌患者登记处。13例患者（13.5%）的14个致病性突变在8个基因中被确定：4个在ATM中，2个在BRCA 2，CHEK 2和MSH6中，1个在BARD 1，BRCA 1，FANCM和NBN中。其中包括已建立的胰腺癌基因中的9个突变（9.4%）。在PDAC一级亲属中发现了3个突变，在乳腺癌、胰腺癌、结直肠癌、卵巢癌或子宫内膜癌一级或二级亲属中发现了10个突变。这些结果表明，相当大比例的PDAC患者携带与其他癌症相关的易感基因的种系突变，并且更好地了解胰腺癌风险将取决于对具有广泛肿瘤群的家族的评估。这些发现强调了对胰腺癌患者生殖细胞基因组检测的建议的必要性。
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 cancer. 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 pancreatic cancer patients.