Division of Gynecologic Oncology, Weill Cornell Medicine, New York, New York.
Genetic Risk Assessment Program, Weill Cornell Medicine, New York, New York.
Cancer. 2019 Mar 1;125(5):690-697. doi: 10.1002/cncr.31856. Epub 2018 Nov 27.
Genetic assessment in Ashkenazi Jewish (AJ) patients often is limited to BRCA1/2 founder mutation testing. With access to time-efficient and cost-efficient multigene panel testing, some advocate expanding genetic testing in this population. However, to the best of the authors' knowledge, rates of nonfounder BRCA1/2 mutations and mutations in cancer-associated genes other than BRCA1/2 among AJ are not known. In the current study, the authors sought to assess the prevalence of mutations other than BRCA1/2 founder mutations among AJ patients undergoing genetic assessment.
The authors reviewed the medical records for all AJ patients who underwent genetic assessment at a single institution between June 2013 and December 2016. Mutations were categorized as 1) BRCA1/2 AJ founder mutations (BRCA1 185delAG, BRCA1 5382insC, or BRCA2 6174delT); 2) nonfounder BRCA1/2 mutations; or 3) mutations in non-BRCA1/2 cancer-associated genes.
A total of 732 AJ patients underwent genetic assessment. Of these, 371 patients (51%) had a personal history of breast or ovarian cancer, 540 patients (73.8%) had a family history of breast cancer, and 132 patients (18%) had a family history of ovarian cancer. In the study population, 101 patients (13.8%) were found to have a pathogenic mutation, 78 patients (10.7%) had a BRCA1/2 founder mutation, 3 patients (0.4%) had a nonfounder BRCA1/2 mutation, and 20 patients (2.7%) had a mutation in a non-BRCA1/2 cancer-associated gene. Non-BRCA1/2 cancer-associated genes harboring mutations included RAD51D, TP53, mutS homolog 6 (MSH6), checkpoint kinase 2 (CHEK2), adenomatous polyposis coli (APC), and Fanconi anemia group C protein (FANCC).
Among AJ patients found to have a pathogenic mutation on genetic assessment, approximately 22.8% had a mutation that would be missed with BRCA1/2 AJ founder mutation testing. Comprehensive multigene panel sequencing can provide clinically relevant genetic information for AJ patients and should be considered for genetic assessment in this population.
对阿什肯纳兹犹太人（AJ）患者进行基因评估时，通常仅限于 BRCA1/2 种系突变检测。随着时间高效且成本高效的多基因面板检测的出现，一些人主张扩大该人群的基因检测。然而，据作者所知，AJ 人群中除 BRCA1/2 以外的非种系 BRCA1/2 突变和癌症相关基因的突变率尚不清楚。在本研究中，作者旨在评估在一家机构接受基因评估的 AJ 患者中，除 BRCA1/2 种系突变以外的突变的发生率。
作者回顾了 2013 年 6 月至 2016 年 12 月期间在一家机构接受基因评估的所有 AJ 患者的病历。将突变分为 1）BRCA1/2 AJ 种系突变（BRCA1 185delAG、BRCA1 5382insC 或 BRCA2 6174delT）；2）非种系 BRCA1/2 突变；或 3）非 BRCA1/2 癌症相关基因中的突变。
共有 732 名 AJ 患者接受了基因评估。其中，371 名患者（51%）有乳腺癌或卵巢癌个人病史，540 名患者（73.8%）有乳腺癌家族史，132 名患者（18%）有卵巢癌家族史。在研究人群中，101 名患者（13.8%）发现有致病性突变，78 名患者（10.7%）有 BRCA1/2 种系突变，3 名患者（0.4%）有非种系 BRCA1/2 突变，20 名患者（2.7%）有非 BRCA1/2 癌症相关基因中的突变。携带突变的非 BRCA1/2 癌症相关基因包括 RAD51D、TP53、mutS 同源物 6（MSH6）、检查点激酶 2（CHEK2）、腺瘤性结肠息肉病（APC）和范可尼贫血组 C 蛋白（FANCC）。
在接受基因评估的发现致病性突变的 AJ 患者中，约 22.8% 的患者存在 BRCA1/2 AJ 种系突变检测会遗漏的突变。全面的多基因面板测序可为 AJ 患者提供具有临床意义的遗传信息，应考虑在该人群中进行基因评估。
