内脏转移性去势抵抗性前列腺癌患者的基因突变特征分析

characteristics of gene mutations in patients with visceral metastatic castration-resistant prostate cancer

目的探讨内脏转移性去势抵抗性前列腺癌(mCRPC-VM)患者的基因突变特征。方法选取2017年1月至2019年12月在温州医科大学附属第一医院泌尿外科确诊为mCRPC-VM的患者33例,均完善前列腺易感基因二代测序。采用生物信息学分析mCRPC-VM患者的基因突变特征,并与SU2C-PCF数据库的444例转移性去势抵抗性前列腺癌患者基因组数据进行比较。结果33例mCRPC-VM患者突变频率从高到低的基因分别为TP53(45.45%)、AR(42.42%)、NCOR2(15.15%)、PTEN(15.15%)、FOXA1(15.15%)、PIK3CA(15.15%)、RB1(15.15%)。3例(9.09%)患者携带胚系突变,均发生于DNA损伤修复通路基因。肝转移患者AR、FOXA1突变频率均高于非肝转移患者(均P<0.05)。TP53、NCOR2、PTEN、FOXA1、PIK3CA突变类型占比最高均为错义突变,AR突变类型占比最高为基因扩增,RB1突变类型占比最高为移码突变。基因缺失突变主要发生在肺转移患者(71.43%),扩增突变主要发生在肝转移患者(66.67%)。与SU2C-PCF数据库比较,本院患者PTEN突变频率明显较低(P<0.05);而AR、TP53、NCOR2、FOXA1、PIK3CA、RB1等基因突变频率比较,差异均无统计学意义(均P>0.05)。结论mCRPC-VM患者的高频率突变基因为TP53、AR,高频率突变基因的类型以错义突变为主。

Objective To investigate the characteristics of gene mutations in patients with viscerally-metastatic castration-resistant prostate cancer(mCRPC-VM).Methods A total of 33 patients diagnosed with mCRPC-VM in the Department of Urology,the First Affiliated Hospital of Wenzhou Medical University from January 2017 to December 2019 were enrolled.The next-generation sequencing of prostate susceptibility genes was performed.Results The mutation frequencies of 33 patients with mCRPC-VM were TP53(45.45%),AR(42.42%),NCOR2(15.15%),PTEN(15.15%),FOXA1(15.15%),PIK3CA(15.15%),and RB1(15.15%).Three patients(9.09%)carried germline mutations,all of which occurred in DNA damage repair pathway genes.The frequencies of AR and FOXA1 mutations in patients with liver metastasis were higher than those in patients without liver metastasis(both P<0.05).The highest proportion of TP53,NCOR2,PTEN,FOXA1 and PIK3CA mutation types were missense mutations,AR mutation types were amplification mutations,and RB1 mutation types were frameshift mutations.The deletion mutations mainly occurred in lung metastasis(71.43%)and amplification mutations mainly occurred in patients with liver metastasis(66.67%).Compared with SU2C-PCF database,the mutation frequency of PTEN in our cohort was significantly lower(P<0.05),while there was no significant difference in the mutation frequency of AR,TP53,NCOR2,FOXA1,PIK3CA and RB1(all P>0.05).Conclusion High-frequency mutations of TP53 and AR have been in patients with mCRPC-VM.The most common type of gene mutations with the highest frequency is missense mutation.