Heterogeneity of genomic profile in patients with HER2-positive breast cancer
Heterogeneity of genomic profile in patients with HER2-positive breast cancer
复制标题
HER2 阳性乳腺癌患者基因组谱的异质性。
DOI：
10.1530/erc-19-0414
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发表时间：
2020-03-01
影响因子：
3.9
通讯作者：
Ning Liao
中科院分区：
文献类型：
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作者：
Bo Chen;Zhang, Guochun;Ning Liao
HER 2阳性乳腺癌是一种生物学和临床异质性疾病。根据激素受体（HR）的表达，乳腺肿瘤可进一步分为HR阳性和HR阴性。在这里，我们阐明了HR+和HR-HER 2阳性乳腺肿瘤的全面体细胞突变谱，以了解其分子异质性。64例HR+/HER 2+和43例HR-/HER 2 + I-III期乳腺癌患者入选本研究。基于捕获的靶向测序使用由520个癌症相关基因组成的面板进行，跨越1.64兆碱基的人类基因组。在107例HER 2阳性患者中共检测到1119个突变。TP 53、CDK 12和PIK 3CA是最常见的突变，突变率分别为76%、61%和49%。与HR-/HER 2+肿瘤相比，HR+/HER 2+肿瘤具有更多的基因扩增、剪接位点和移码突变，以及较少数量的错义、无义和插入-缺失突变。在KEGG分析中，HR+/HER 2+肿瘤在参与同源重组（P=0.004）、TGF-β（P=0.007）和WNT（P=0.002）信号传导途径的基因中的突变多于HR-/HER 2+肿瘤。此外，我们的队列与来自癌症基因组图谱和乳腺癌国际联盟分子分类学的数据集的比较分析揭示了中国HER 2阳性乳腺癌患者独特的体细胞突变谱。我们的研究揭示了中国乳腺癌患者HR+/HER 2+和HR-/HER 2+之间的体细胞突变的异质性。不同的突变谱和相关途径在为该患者子集制定最佳治疗策略方面具有潜在相关性。
HER2-positive breast cancer is a biologically and clinically heterogeneous disease. Based on the expression of hormone receptors (HR), breast tumors can be further categorized into HR-positive and HR-negative. Here, we elucidated the comprehensive somatic mutation profile of HR+ and HR- HER2-positive breast tumors to understand their molecular heterogeneity. Sixty-four HR+/HER2+ and forty-three HR-/HER2+ stage I-III breast cancer patients were included in the study. Capture-based targeted sequencing was performed using a panel consisting of 520 cancer-related genes, spanning 1.64 megabases of the human genome. A total of 1119 mutations were detected among the 107 HER2-positive patients. TP53, CDK12 and PIK3CA were the most frequently mutated, with mutation rates of 76%, 61% and 49%, respectively. HR+/HER2+ tumors had more gene amplification, splice site and frameshift mutations, and a smaller number of missense, nonsense and insertion-deletion mutations than HR-/HER2+ tumors. In KEGG analysis, HR+/HER2+ tumors had more mutations in genes involved in homologous recombination (P=0.004), TGF-beta (P=0.007) and WNT (P=0.002) signaling pathways than HR-/HER2+ tumors. Moreover, comparative analysis of our cohort with datasets from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium revealed the distinct somatic mutation profile of Chinese HER2-positive breast cancer patients. Our study revealed the heterogeneity of somatic mutations between HR+/HER2+ and HR-/HER2+ in Chinese breast cancer patients. The distinct mutation profile and related pathways are potentially relevant in the development of optimal treatment strategies for this subset of patients.