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目的研究乳腺癌易感基因BRCA1和BRCA2在早发性乳腺癌(确诊年龄≤35岁)患者中突变情况,分析致病突变与临床特征之间关系。方法选择2014年9月至2016年6月期间就诊于军事医学科学院附属医院的早发性乳腺癌患者74例,采用高通量二代测序技术以及生物信息分析,对纳入患者BRCA1和BRCA2基因的49个外显子序列及拼接区序列进行检测分析,并将患者按临床特征分组,X~2检验比较BRCA1和BRCA2致病突变在各组的分布。结果在74例早发性乳腺癌患者中,检测到15例(20.27%)BRCA1/2致病突变,包括5例(6.76%)BRCA1致病突变,10例(13.51%)BRCA2致病突变。其中11例为新发现致病突变,检测到1例患者携带相对高频致病基因突变BRCA1∶c.5470_5477delTGCCCAAT。有乳腺癌或卵巢癌家族史组携带致病突变率明显高于无家族史组(40.91%vs 11.54%,X~2=6.534,P=0.011)。结论 BRCA1/2致病突变对早发性乳腺癌意义重大,尤其是伴有乳腺癌或卵巢癌家族史的早发性乳腺癌。新发现的致病突变可能为中国人群特有突变。BRCA1∶c.5470_5477delTGCCCAAT可能成为中国人群的始祖突变。
Objective To investigate the mutations of breast cancer susceptibility genes BRCA1 and BRCA2 in patients with early-stage breast cancer (defined as ≤35 years of age) and to analyze the relationship between pathogenic mutations and clinical features. Methods Seventy-four patients with early-onset breast cancer who were admitted to the Affiliated Hospital of Academy of Military Medical Sciences between September 2014 and June 2016 were selected. High-throughput second-generation sequencing and bioinformatics analysis were used to evaluate the efficacy of BRCA1 and BRCA2 49 exon sequences and splicing region sequences were detected and analyzed, and patients were grouped according to clinical features, X ~ 2 test BRCA1 and BRCA2 pathogenic mutations in the distribution of each group. Results Fifteen cases (20.27%) of BRCA1 / 2 pathogenic mutations were detected in 74 cases of early-onset breast cancer, including 5 cases (6.76%) of BRCA1 causative mutations and 10 cases (13.51%) of BRCA2 causative mutations. Of the 11 cases, newly discovered pathogenic mutations were detected, and one patient was found to have the mutation BRCA1: c.5470_5477delTGCCCAAT. The incidence of pathogenic mutation in the family history group with breast cancer or ovarian cancer was significantly higher than that in the family history group (40.91% vs 11.54%, X ~ 2 = 6.534, P = 0.011). Conclusion The BRCA1 / 2 pathogenic mutation is of great significance to early-stage breast cancer, especially early-stage breast cancer with a family history of breast cancer or ovarian cancer. The newly discovered disease-causing mutations may be unique mutations in the Chinese population. BRCA1: c.5470_5477delTGCCCAAT may be the first ancestor mutation in Chinese population.