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共济失调毛细血管扩张症（ATM）又称毛细血管扩张性共济失调综合征，属于常染色体隐性遗传病，高发于ATM基因突变携带者，表现为共济失调、毛细血管扩张、鼻窦和呼吸道反复感染、免疫缺陷、辐射敏感性、肿瘤易感性增加增加。对于未携带乳腺癌易感基因（BRCA）突变的女性，携带与未携带ATM基因突变相比，乳腺癌风险大约高一倍。不过，ATM基因突变相关乳腺癌的表现类型尚不明确。 2019年1月3日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表北京大学肿瘤医院杨志国、欧阳涛、李金峰、王天峰、范照青、范铁、林本耀、张娟、解云涛等学者的研究报告，调查了中国BRCA基因突变阴性乳腺癌患者的ATM基因生殖系突变发生率和临床特征。 该单中心大数据研究对2003年10月～2015年5月北京大学肿瘤医院7657例BRCA基因突变阴性乳腺癌患者的62基因检测结果进行回顾分析，筛查ATM基因生殖系突变。通过独立的聚合酶链反应扩增和双脱氧链终止法测序，对所有有害突变进行验证。 结果，发现ATM基因突变携带者30例，ATM基因突变发生率为0.4%，携带ATM基因致病突变31种（其中一例携带2种致病突变）。大多数突变（28种，占90.3%）为无义突变或移码突变。对于所有ATM基因突变，新发现突变19种，占61.3%，频发突变13种，占41.9%。 ATM基因突变的携带者与未携带者相比：
因此，中国BRCA基因突变阴性乳腺癌的ATM基因突变发生率大约0.4%，ATM基因突变携带者的癌症家族史、雌激素受体、孕激素受体、淋巴结阳性乳腺癌比例较高。 Breast Cancer Res Treat. 2019 Jan 3. Prevalence and characterization of ATM germline mutations in Chinese BRCA1/2-negative breast cancer patients. Yang Z, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, Zhang J, Xie Y. Peking University Cancer Hospital & Institute, Beijing, China. 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. KEYWORDS: ATM gene Germline mutation Breast cancer Chinese population PMID: 30607632 DOI: 10.1007/s10549-018-05124-5
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