二代测序检测乳腺癌PIK3CA、TP53、PTEN基因突变及其临床意义

Detection and clinical significance of PIK3CA, TP53, PTEN genes mutation in breast cancer on next-generation sequencing

目的:研究二代测序(NGS)检测乳腺癌磷脂酰肌醇激酶-3催化亚基α基因(PIK3CA)、肿瘤蛋白p53基因(TP53)、人第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)的突变及临床意义。方法:收集2015年7月—2018年12月苏州大学附属第一医院的81例乳腺癌组织。使用基于NGS的108基因panel对PIK3CA、TP53、PTEN这3个突变率最高的基因进行基因状态检测,再结合患者病理及临床资料进行分析。结果:在81例乳腺癌标本中,PIK3CA基因突变率为58.02%,TP53基因突变率为60.49%,PTEN基因突变率为11.11%。3个基因总突变率为87.65%。PIK3CA基因突变率与乳腺癌患者相关临床病理因素无明显相关(P>0.05)。ER阴性或PR阴性或HER-2阳性的患者更容易出现TP53基因突变(P=0.001、0.002、0.028);组织学分级差的患者更易伴随TP53突变(P<0.001);Ki67≥15%的患者更容易伴随TP53突变(P=0.022)。PTEN基因突变率与PR阴性有关(P=0.025)。结论:TP53突变与ER或PR阴性、组织学分级较差、Ki67较高有关,提示预后较差。NGS作为近两年发展起来的一种比较先进的测序方法,可有效筛选乳腺癌相关基因突变,为临床医师提供有效信息,由此促进乳腺癌迈入精准治疗,改善患者预后。

Objective:To study the mutation of PIK3CA, TP53, PTEN genes in breast cancer detected by next-generation sequencing(NGS), and to explore the clinical significance. Methods:Took 81 cases of tumor tissues of breast cancer patients treated in the First Affiliated Hospital of Suzhou University from July 2015 to November 2018. The gene states of PIK3CA, TP53 and PTEN with the highest mutation rates were detected by using 108 gene panel based on NGS. Pathological data and clinical data were analyzed. Results:In 81 cases of breast cancer, the mutation rate of PIK3CA gene was 58.02%;the mutation rate of TP53 gene was 60.49%;the mutation rate of PTEN gene mutation was 11.11%, and the total mutation rate of three genes was 87.65%. The mutation rate of PIK3CA was not significantly correlated with clinical related factors(P>0.05). TP53 mutation was more likely in ER negative or PR negative or HER-2 positive patients(P=0.001, 0.002, 0.028);TP53 mutation was more likely in patients with poor histological grade(P<0.001);TP53 mutation was more likely in patients with Ki67 >15%(P=0.022). The mutation rate of PTEN gene was related to PR negative(P=0.025). Conclusion:The incidence of TP53 mutation was higher in ER or PR negative,high histological grade or high ki67 patients, suggesting poor prognosis. As an advanced sequencing method developed in recent two years, NGS can effectively screen breast cancer-related gene mutations and provide effective information for clinicians, so as to formulate individualized treatment programs for patients and improve their prognosis.