高通量测序技术检测乳腺癌患者BRCA1、BRCA2基因的意义

doi:10.3969/j.issn.1673-8640.2019.11.015

摘要/Abstract

摘要：

目的采用高通量测序技术检测乳腺癌易感基因（BRCA）1和BRCA2,并探讨BRCA1、BRCA2在家族性乳腺癌筛查中的意义。方法选取7例女性乳腺癌患者及12名健康女性,采用高通量测序技术对BRCA1、BRCA2基因进行测序分析,用Sanger测序法验证检出的位点并对新发BRCA1基因突变位点携带者的家庭成员进行检测。结果 7例乳腺癌患者中,检测出1例致病性突变BRCA2（c.5073dupA）,1例可能致病的突变BRCA1（c.3343G>T）及1例临床未明意义的突变BRCA2（c.1211A>T）;12名健康女性中均未检测出BRCA1、BRCA2基因的可疑致病突变位点;携带BRCA1（c.3343G>T）突变的家系中有2名乳腺癌患者。结论 BRCA1（c.3343G>T）是首次发现的遗传性乳腺癌的可能致病性变异位点,其携带者家系中乳腺癌发病率明显升高,建议对其他携带者加强随访,尽早进行手术或药物干预。

关键词: 乳腺癌易感基因1, 乳腺癌易感基因2, 新发基因突变, 家族性乳腺癌

Abstract:

Objective To determine the breast cancer susceptibility protien（BRCA）1 and BRCA2 genes by next-generation sequencing,and to investigate the roles of BRCA1 and BRCA2 in screening familial bresst cancer. Methods Totally,7 female breast cancer patients and 12 healthy females without the family history of breast cancer were enrolled. All participants received BRCA1 and BRCA2 gene determinations using next-generation sequencing,and all mutations in the probands were confirmed with Sanger sequencing. The family mumbers of the patient who carried BRCA1 mutation had been determined for the same gene site. Results Of the 7 patients,there was 1 case of BRCA2（c.5073dupA） pathogenic mutation,1 case of BRCA1（c.3343G>T） likely pathogenic mutation and 1 case of BRCA2（c.1211A>T） variant of uncertain significance mutation. None of suspicious mutation was found in healthy females. In the family carrying BRCA1（c.3343G>T）,2 cases of breast cancer were found. Conclusions BRCA1（c.3343G>T） has firstly been reported. The family carrying this site shows a high incidence of breast cancer. Therefore,close follow-ups and surgical and drug intervention are recommended for the first-degree relatives of breast cancer patients.

Key words: Breast cancer susceptibility protein 1 gene, Breast cancer susceptibility protein 2 gene, New gene mutation, Familial breast cancer

中图分类号:

R446.1

李金洁, 刁艳君, 李蕊, 苏明权, 马越云, 郝晓柯, 杨柳. 高通量测序技术检测乳腺癌患者BRCA1、BRCA2基因的意义[J]. 检验医学, 2019, 34(11): 1026-1031.

LI Jinjie, DIAO Yanjun, LI Rui, SU Mingquan, MA Yueyun, HAO Xiaoke, YANG Liu. BRCA1 and BRCA2 gene determinations in breast cancer patients by next-generation sequencing[J]. Laboratory Medicine, 2019, 34(11): 1026-1031.

图/表 6

参考文献 20

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基因	例数	位置	突变	氨基酸改变	突变类型
BRCA1	1	17：41244205	c.3343G>T	Glu1115Ter	无义突变
BRCA2	4	13：32907327	c.1712_1713insA	Val572CysfsTer18	移码突变
	1	13：32913782	c.5290_5292delTCAinsTAC	Ser1764Tyr	错义突变
	1	13：32907326	c.1711T>C	Ser571Pro	错义突变
	1	13：32907327	c.1712C>A	Ser571Tyr	错义突变
	1	13：32906826	c.1211A>T	Asn404Ile	错义突变
	1	13：32913558	c.5073dupA	Trp1692MetfsTer3	移码突变

基因	例数	位置	突变	氨基酸改变	突变类型
BRCA1	1	17：41244205	c.3343G>T	Glu1115Ter	无义突变
BRCA2	4	13：32907327	c.1712_1713insA	Val572CysfsTer18	移码突变
	1	13：32913782	c.5290_5292delTCAinsTAC	Ser1764Tyr	错义突变
	1	13：32907326	c.1711T>C	Ser571Pro	错义突变
	1	13：32907327	c.1712C>A	Ser571Tyr	错义突变
	1	13：32906826	c.1211A>T	Asn404Ile	错义突变
	1	13：32913558	c.5073dupA	Trp1692MetfsTer3	移码突变

项目	BRCA1 c.3343G>T	BRCA2 c.1211A>T	BRCA2 c.5073dupA
突变类型	无义突变	错义突变	移码突变
最小等位基因频率的最大值	未获得	0.001 4	未获得
软件预测	（可能）有害	（可能）有害	未获得
报道情况	未见报道	未见报道	参考文献（9~15）
家族史	妹妹40岁患乳腺癌45岁患卵巢癌	未获得	未获得
结论	可能致病性	临床意义未明	致病性

项目	BRCA1 c.3343G>T	BRCA2 c.1211A>T	BRCA2 c.5073dupA
突变类型	无义突变	错义突变	移码突变
最小等位基因频率的最大值	未获得	0.001 4	未获得
软件预测	（可能）有害	（可能）有害	未获得
报道情况	未见报道	未见报道	参考文献（9~15）
家族史	妹妹40岁患乳腺癌45岁患卵巢癌	未获得	未获得
结论	可能致病性	临床意义未明	致病性