Prevalence and characterization of ATM germline mutations in Chinese BRCA1/2-negative breast cancer patients
Prevalence and characterization of ATM germline mutations in Chinese BRCA1/2-negative breast cancer patients
复制标题
中国BRCA1/2阴性乳腺癌患者ATM种系突变的患病率和特征
DOI：
10.1007/s10549-018-05124-5
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发表时间：
2019
影响因子：
3.8
通讯作者：
Xie Yuntao
中科院分区：
文献类型：
--
作者：
Yang Ziguo;Ouyang Tao;Li Jinfeng;Wang Tianfeng;Fan Zhaoqing;Fan Tie;Lin Benyao;Zhang Juan;Xie Yuntao
目的：共济失调毛细血管扩张突变基因（ATM）是乳腺癌的中度易感基因。然而，很少有人知道与ATM突变相关的乳腺癌表型。因此，我们调查了ATM种系突变的频谱和临床特点，在中国乳腺癌patient.Methods：一个多基因面板进行筛选ATM种系突变7657 BRCA 1/2阴性乳腺癌患者。所有有害突变均通过独立聚合酶链反应（PCR）-桑格测序进行验证。结果：在30名携带者中共发现ATM基因31个致病突变，该队列的ATM突变率为0.4%（30/7，657）。绝大多数突变（90.3%，28/31）为无义突变或移码突变。在所有的ATM突变中，61.3%（19/31）为新突变，13例为复发突变，ATM突变携带者更易有乳腺癌和/或卵巢癌家族史（携带者26.7%对非携带者8.6%，p < 0.001），以及任何癌症家族史（携带者60.0%对非携带者31.5%，p = 0.001）。此外，ATM突变携带者更可能有雌激素受体（ER）阳性（p = 0.011），孕激素受体（PR）阳性（p = 0.040），淋巴结阳性乳腺癌（p = 0.034）。结论：ATM突变的患病率约为0.4%，在中国BRCA 1/2阴性乳腺癌。ATM突变携带者更有可能有癌症家族史，并发展为ER和/或PR阳性乳腺癌或淋巴结阳性乳腺癌。
Purpose:The ataxia telangiectasia-mutated (ATM) gene is a moderate susceptibility gene for breast cancer. However, little is known about the breast cancer phenotypes associated with ATM mutation. We therefore investigated the spectrum and clinical characteristics of ATM germline mutations in Chinese breast cancer patients.Methods:A multi-gene panel was performed to screen for ATM germline mutations in 7657 BRCA1/2-negative breast cancer patients. All deleterious mutations were validated by independent polymerase chain reaction (PCR)-Sanger sequencing.Results:A total of 31 pathogenic mutations in the ATM gene across 30 carriers were identified, and the ATM mutation rate was 0.4% (30/7,657) in this cohort. The majority of the mutations (90.3%, 28/31) were nonsense or frameshift mutations. Of the total ATM mutations, 61.3% (19/31) were novel mutations and 13 recurrent mutations were found. ATM mutations carriers were significantly more likely to have a family history of breast and/or ovarian cancer (26.7% in carriers vs. 8.6% in non-carriers, p < 0.001), as well as a family history of any cancer (60.0% in carriers vs. 31.5% in non-carriers, p = 0.001). In addition, ATM mutations carriers were significantly more likely to have oestrogen receptor (ER)-positive (p = 0.011), progesterone receptor (PR)-positive (p = 0.040), and lymph node-positive breast cancer (p = 0.034).Conclusions:The prevalence of the ATM mutation is approximately 0.4% in Chinese BRCA1/2-negative breast cancer. ATM mutation carriers are significantly more likely to have a family history of cancer and to develop ER- and/or PR-positive breast cancer or lymph node-positive breast cancer.