Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer
Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer
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DOI：
10.1007/s10549-015-3293-7
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发表时间：
2015-02-01
影响因子：
3.8
通讯作者：
Scott, Rodney J.
中科院分区：
文献类型：
--
作者：
Wong-Brown, Michelle W.;Meldrum, Cliff J.;Scott, Rodney J.
三阴性乳腺癌（TNBC）缺乏雌激素、孕激素和HER2受体的表达。tnbc的基因表达谱与BRCA1突变女性的乳腺肿瘤相似。迄今为止的报告表明，多达20%的TNBC患者携带种系BRCA突变；然而，在不同的国家和不同的研究中，TNBC患者中BRCA突变的患病率差异很大。我们研究了774名患有三阴性乳腺癌的女性，平均诊断年龄为58.0岁。基因组DNA样本由澳大利亚乳腺癌组织库（ABCTB）（439名患者）和博美拉尼亚医科大学遗传和病理学系（335名患者）提供。对BRCA1和BRCA2的整个编码区和外显子-内含子边界进行扩增和测序。我们在774例（9.6%）三阴性患者中鉴定出74例BRCA1或BRCA2突变。突变流行率在澳大利亚为9.3%，在波兰为9.9%。在这两个国家，BRCA1突变携带者的平均诊断年龄明显低于非携带者，而BRCA2突变携带者的发病年龄与非携带者相似。在澳大利亚的队列中，59%的突变阳性患者没有乳腺癌或卵巢癌的家族史，因此不具备进行基因检测的资格。三阴性表型应作为一项标准增加到遗传筛查指南。
Triple-negative breast cancers (TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles of TNBCs are similar to those of breast tumours in women with BRCA1 mutations. Reports to date indicate that up to 20 % of TNBC patients harbour germline BRCA mutations; however, the prevalence of BRCA mutations in TNBC patients varies widely between countries and from study to study. We studied 774 women with triple-negative breast cancer, diagnosed on average at age 58.0 years. Samples of genomic DNA were provided by the Australian Breast Cancer Tissue Bank (ABCTB) (439 patients) and by the Department of Genetics and Pathology of the Pomeranian Medical University (335 patients). The entire coding regions and the exon-intron boundaries of BRCA1 and BRCA2 were amplified and sequenced by next-generation sequencing. We identified a BRCA1 or BRCA2 mutation in 74 of 774 (9.6 %) triple-negative patients. The mutation prevalence was 9.3 % in Australia and was 9.9 % in Poland. In both countries, the mean age of diagnoses of BRCA1 mutation carriers was significantly lower than that of non-carriers, while the age of onset of BRCA2 mutation carriers was similar to that of non-carriers. In the Australian cohort, 59 % of the mutation-positive patients did not have a family history of breast or ovarian cancer, and would not have qualified for genetic testing. The triple-negative phenotype should be added as a criterion to genetic screening guidelines.