基于下一代测序技术的乳腺癌常染色体拷贝数变异检测

Detection of autosomal CNV in breast cancer based on next generation sequencing

目的探讨下一代测序(NGS)技术检测乳腺癌组织中常染色体拷贝数变异(CNV)的临床意义及分析17号染色体CNV与人表皮生长因子受体2(HER-2)基因。方法收集20例免疫组化(IHC)结果为3+的乳腺浸润性导管癌组织样本,采用NGS检测所有常染色体的CNV及HER-2基因扩增情况。结果20例乳腺癌组织样本中CNV发生频率较高的染色体区域为17q、8q2、1q2/1q4、11q1、10q2、20q1、1p3、2p2、8p1、15q2以及16p1;发现CNV发生频率与年龄相关(r=0.541,P=0.014)。当HER-2 IHC结果3+时,17号染色体CNV发生频率较高,HER-2基因存在一定比例扩增,但17号染色体CNV发生频率与HER-2基因的扩增,差异无统计学意义(χ^2=0.808,P=0.189)。结论NGS可以一次性全面检测乳腺癌组织中常染色体的CNV及HER-2基因的扩增情况,可以作为研究CNV及HER-2扩增在乳腺癌发生、发展中的作用机制,HER-2基因扩增结果可为指导临床治疗和判断预后提供参考。

Objective To explore the clinical significance of autosomal copy number variations(CNV)in breast cancer and analyze the correlation between CNV on chromosome 17 and human epidermal growth factor receptor 2(HER-2)gene amplification by NGS.Methods Twenty cases of invasive ductal breast cancer with 3+immunohistochemistry(IHC)results were enrolled and detected by NGS to analyze CNV and the amplification of HER-2 genes.Results The high frequency regions of CNV in 20 samples were 17q,8q2,1q2/1q4,11q1,10q2,20q1,1p3,2p2,8p1,15q2 and 16p1.Further statistical analysis showed that the frequency of CNV was age-related(r=0.541,P=0.014).And the research results revealed that the frequency of CNV on chromosome 17 was high and HER-2 gene amplification when IHC result of HER-2 was 3+;However,there was no significant difference between the frequency of CNV on chromosome 17 and the amplification of HER-2 gene(χ^2=0.808,P=0.189).Conclusion NGS can comprehensively detect the CNV and the amplification of HER-2 genes in one test,which is helpful to illuminate the mechanism of breast cancer and provide reference for clinical treatment and prognosis.