乳腺浸润性导管癌BRCA1/2基因变异与肿瘤突变负荷相关

doi:10.3969/j.issn.1009-976X.2020.03.019

岭南现代临床外科 ›› 2020, Vol. 20 ›› Issue (03): 350-354.DOI: 10.3969/j.issn.1009-976X.2020.03.019

乳腺浸润性导管癌BRCA1/2基因变异与肿瘤突变负荷相关

廖健伟¹, 吴畏², 李晓娟¹, 萧晓琴¹, 蒋圆玲¹, 彭小芳¹, 欧阳能太^1,*

中山大学孙逸仙纪念医院 1.细胞分子诊断中心; 2.乳腺肿瘤医学部,广州510120

通讯作者: *欧阳能太,Email: ouynt@mail.sysu.edu.cn
基金资助:
国家自然青年科学基金（81903043）; 广东省自然科学基金（2018A030310086）

BRCA1/2 gene mutation is correlated with tumor mutation burden in breast invasive ductal carcinoma

LIAO Jianwei¹, WU Wei², LI Xiao-juan¹, XIAO Xiao-qin¹, JIANG Yuan-lin¹, PENG Xiao-fang¹, OUYANG Neng-tai¹

1. Cellular and Molecular Diagnosis Center;
2. Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China

Received:2020-05-07 Online:2020-06-20 Published:2020-06-20
Contact: Ouyang Neng-tai, ouynt@mail.sysu.edu.cn

摘要/Abstract

摘要： 目的初步分析乳腺浸润性导管癌中的基因变异与肿瘤突变负荷（Tumor mutation burden, TMB）的关系,为发现免疫疗效预测因子提供参考。方法本研究主要通过免疫组化联合杂交捕获高通量测序技术,以ER、PR、HER2作为标志物进行分组,对32例乳腺浸润性导管癌进行多基因变异分析,包括体细胞变异、胚系变异、微卫星不稳定状态、肿瘤突变负荷等。结果 32例乳腺浸润性导管癌中三阴型4例,HER2阳性型4例,其余激素受体（hormone receptor）阳性型（包括Luminal A和B）24例。32例标本中TP53失活突变、PIK3CA激活突变发生率最高,分别为84.4%和50.0%,未发现微卫星高度不稳定（Microsatellite Instability-High, MSI-H）病例,TMB值大于等于5的18例,BRCA1/2突变的6例。TMB与受体分型、是否TP53突变或PIK3CA突变均无关,而与BRCA1/2突变状态有关,携带BRCA1/2突变的患者TMB为11.9±9.73,不携带BRCA1/2突变的患者TMB为5.62±3.67,两者具有明显区别。结论携带BRCA1/2的乳腺浸润性导管癌具有更高的TMB。

关键词: PIK3CA, 高通量测序, BRCA1/2, 浸润性导管癌, TMB

Abstract: Objective To provide reference for uncovering biomarkers for immunotherapy,we investigated the correlation between multiple gene mutationswith tumor mutation burden （TMB） in invasive ductal carcinoma of breast. Methods 32 cases were grouped by ER, PR and HER2 status using immunohistochemistry. Then target capture sequencing was applied to analyze gene variants including somatic variant, germline variant, microsatellite instability and tumor mutation burden. Results Four cases are triple negative, four cases are HER2 positive alone, and other 24 cases are hormone receptor positive types （including Luminal A and B）. The two most common mutations are loss-of-function mutation of TP53 and gain-of-function mutation of PIK3CA, with incidence rates 84.4% and 50.0%, respectively. No MSI-H cases are found. There are 18 cases with TMB value greater than or equal to 5. Only 6 cases are found BRCA1/2 mutated. TMB is not correlated to receptor classification, TP53 mutation or PIK3CA mutation, but is related to BRCA1/2 mutation. TMB of BRCA1/2 mutated cases is 11.9±9.73, while that of cases without BRCA1/2 mutation is 5.62±3.67. Higher TMB is found in cases with BRCA1/2 gene mutations. Conclusion The invasive ductal carcinoma of breast with BRCA1/2 has higher TMB.

Key words: BRCA1/2, invasive ductal carcinoma, TMB, PIK3CA, NGS

中图分类号:

R737.9

廖健伟, 吴畏, 李晓娟, 萧晓琴, 蒋圆玲, 彭小芳, 欧阳能太. 乳腺浸润性导管癌BRCA1/2基因变异与肿瘤突变负荷相关[J]. 岭南现代临床外科, 2020, 20(03): 350-354.

LIAO Jianwei, WU Wei, LI Xiao-juan, XIAO Xiao-qin, JIANG Yuan-lin, PENG Xiao-fang, OUYANG Neng-tai. BRCA1/2 gene mutation is correlated with tumor mutation burden in breast invasive ductal carcinoma[J]. Lingnan Modern Clinics in Surgery, 2020, 20(03): 350-354.

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乳腺浸润性导管癌BRCA1/2基因变异与肿瘤突变负荷相关

BRCA1/2 gene mutation is correlated with tumor mutation burden in breast invasive ductal carcinoma

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