The Detection And Clinical Significance Of PIK3CA,TP53,PTEN Genes Mutation In Breast Cancer On Next-generation Sequencing

Objcet:To study the mutation and heterogeneity of PIK3CA,TP53,PTEN genes in breast cancer detected by next-generation sequencing,and to explore the clinical significance of mutation,so as to provide theoretical basis for clinical diagnosis and treatment into individualization.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.After parafin embedding,the tumor tissue was cutted with the method of manual microdissection.The gene states of PIK3CA,TP53 and PTEN were detected by using 108 gene panel based on NGS.The mutation,rearrangement and increase of copy number were analyzed.Pathological data such as estrogen level(ER),progesterone level(PR),human epidermal growth factor receptor 2(Her-2),Ki67 and other clinical data were analyzed.Results:(1)In 81 cases of breast cancer,47 cases had PIK3CA gene mutation,the mutation rate was 58.02%;49 cases had TP53 gene mutation,the mutation rate was 60.49%;9 cases had PTEN gene mutation,the mutation rate was 11.1%,and the total mutation rate of three genes was 87.65%.The high rates of TP53 and PIK3CA mutations were mainly considered to be related to the mechanism of breast cancer.(2)According to the immunohistochemical status of ER,PR and Ki67.breast cancer was classified into four molecular subtypes:LuminalA,LuminalB,HER-2 overexpression and TNBC.The main clinical diagnosis and histological grade were invasive ductal carcinoma and WHO Ⅱ grade.Among patients with PIK3CA mutation,LuminalA subtype accounts for 22 cases(46.8%),LuminalB subtype accounts for 6 cases(12.8%),HER-2 overexpression subtype accounts for 16 cases(34.0%)and TNBC subtype accounts for 3 cases(6.4%).Among patients with TP53 mutation,LuminalA subtype accounts for 14 cases(28.6%),LuminalB subtype accounts for 6 cases(12.2%),HER-2 overexpression subtype accounts for 19 cases(38.8%)and TNBC subtype accounts for 10 cases(20.4%).Among patients with PTEN mutations,LuminalA subtype accounts for 0 cases(0%),LuminalB subtype accounts for 3 cases(33.3%),HER-2 overexpression subtype accounts for 3 cases(33.3%)and TNBC subtype accounts for 3 cases(33.3%).(3)All PIK3CA mutations were missense mutations.TP53 mutations included missense mutation,nonsense mutation,splicing mutation,truncating mutation,frameshift mutation,of which 28 were missense mutation,reaching 27.1%.PTEN mutations included missense mutation,truncating mutation and frameshift mutation,and truncating mutation was the main mutation(55.6%).(4)The mutation rate of PIK3CA was not significantly correlated with sex,age,lymph node metastasis,distant metastasis,clinical stage and so on.But the rate of TP53 mutation was related to ER and/or PR and/or HER-2 condition(p value were 0.001.0.002 and 0,028),histological grade(p value was 0.000)and KI67(p value wsls 0.022).The rate of PTEN mutation was related to PR condition(p value were 0.025).The mutation rates of PIK3CA,TP53 and PTEN genes had no relationship with each other.Cases with both TP53 and PIK3CA mutation had poor outcome.Conclusion:Breast cancer is a heterogeneous disease with different histological and pathological characteristics,complex molecular biological characteristics and various genetic and epigenetic mutations.The incidence of TP53 mutation was higher in ER or PR negative,high histological grade or high ki67 patients,suggesting poor prognosis.Cases with both TP53 and PIK3CA mutation had poor outcome.As an advanced sequencing method developed in recent two years,next-generation sequencing 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.