Frequency of Mutations in Individuals With Breast Cancer Referred for BRCA1 and BRCA2 Testing Using Next-Generation Sequencing With a 25-Gene Panel
Frequency of Mutations in Individuals With Breast Cancer Referred for BRCA1 and BRCA2 Testing Using Next-Generation Sequencing With a 25-Gene Panel
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DOI：
10.1002/cncr.29010
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发表时间：
2015-01-01
期刊：
影响因子：
6.2
通讯作者：
Hartman, Anne-Renee
中科院分区：
文献类型：
--
作者：
Tung, Nadine;Battelli, Chiara;Hartman, Anne-Renee
背景下一代测序（NGS）允许同时对多个癌症易感性基因进行测序，并且对于个体而言，可能比序贯测试更有效且更便宜。作者使用一组与遗传性癌症易感性相关的 25 个基因，评估了被转诊进行 BRCA1 和 BRCA2 (BRCA1/2) 基因检测的乳腺癌个体中有害种系突变的频率。 方法这是一项使用 NGS 对 2158 名个体进行的横断面研究，其中包括 1781 名被转诊进行商业 BRCA1/2 基因检测（队列 1）和 377 名有详细个人资料的个体。 和家族史，并且之前 BRCA1/2 突变检测呈阴性（队列 2）。结果 在 16 个基因中发现突变，最常见的是 BRCA1、BRCA2、CHEK2、ATM 和 PALB2。在队列 1 的参与者中，9.3% 的人携带 BRCA1/2 突变，3.9% 的人携带另一个乳腺癌/卵巢癌易感基因的突变，0.3% 的人携带另一个与乳腺癌或卵巢癌无关的癌症易感基因的偶然突变。在队列 2 中，除 BRCA1/2 之外的乳腺/卵巢相关基因突变频率为 2.9%，另外 0.8% 存在偶然突变。在队列 1 中，在 7 名个体中发现了与林奇综合征相关的突变。与 BRCA1/2 突变相反，乳腺癌诊断时的年龄和卵巢癌或年轻乳腺癌家族史都不能预测其他突变。与非德系犹太人相比，德系犹太人中除 BRCA1/2 以外的基因突变频率较低 (P=.026)。结论使用 NGS 25 基因组，除 BRCA1/2 以外的基因突变频率为 4.3%，大多数突变 (3.9%) 是在与乳腺癌/卵巢癌相关的基因中发现的。癌症 2015 年；121：25-33。 (c) 2014年美国癌症协会。使用下一代测序25基因panel，乳腺癌患者除BRCA1/2以外的基因突变频率为4.3%，其中大多数突变（3.9%）发生在与乳腺癌/卵巢癌相关的基因中。大约一半的 BRCA1/2 以外基因突变的患者被鉴定为中等外显率基因，而这些基因的医疗管理效果尚不明确。
BACKGROUNDNext-generation sequencing (NGS) allows for simultaneous sequencing of multiple cancer susceptibility genes and, for an individual, may be more efficient and less expensive than sequential testing. The authors assessed the frequency of deleterious germline mutations among individuals with breast cancer who were referred for BRCA1 and BRCA2 (BRCA1/2) gene testing using a panel of 25 genes associated with inherited cancer predisposition.METHODSThis was a cross-sectional study using NGS in 2158 individuals, including 1781 who were referred for commercial BRCA1/2 gene testing (cohort 1) and 377 who had detailed personal and family history and had previously tested negative for BRCA1/2 mutations (cohort 2).RESULTSMutations were identified in 16 genes, most frequently in BRCA1, BRCA2, CHEK2, ATM, and PALB2. Among the participants in cohort 1, 9.3% carried a BRCA1/2 mutation, 3.9% carried a mutation in another breast/ovarian cancer susceptibility gene, and 0.3% carried an incidental mutation in another cancer susceptibility gene unrelated to breast or ovarian cancer. In cohort 2, the frequency of mutations in breast/ovarian-associated genes other than BRCA1/2 was 2.9%, and an additional 0.8% had an incidental mutation. In cohort 1, Lynch syndrome-related mutations were identified in 7 individuals. In contrast to BRCA1/2 mutations, neither age at breast cancer diagnosis nor family history of ovarian or young breast cancer predicted for other mutations. The frequency of mutations in genes other than BRCA1/2 was lower in Ashkenazi Jews compared with non-Ashkenazi individuals (P=.026).CONCLUSIONSUsing an NGS 25-gene panel, the frequency of mutations in genes other than BRCA1/2 was 4.3%, and most mutations (3.9%) were identified in genes associated with breast/ovarian cancer. Cancer 2015;121:25-33. (c) 2014 American Cancer Society.Using a next-generation sequencing 25-gene panel, the frequency of mutations for patients with breast cancer in genes other than BRCA1/2 is 4.3%, and most of the mutations (3.9%) are in genes associated with breast/ovarian cancer. Approximately half of patients with mutations in genes other than BRCA1/2 are identified in moderate-penetrance genes for which the efficacy of medical management is less well defined.