Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
First College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.
Int J Cancer. 2020 Jun 15;146(12):3369-3378. doi: 10.1002/ijc.32961. Epub 2020 Mar 25.
Prostate cancer is a heterogeneous disease and optimum gene targeting treatment is often impermissible. We aim to determine the intratumoral genomic heterogeneity of prostate cancer and explore candidate genes for targeted therapy. Exome sequencing was performed on 37 samples from 16 patients with prostate cancer. Somatic variant analysis, copy number variant (CNV) analysis, clonal evolution analysis and variant spectrum analysis were used to study the intratumoral genomic heterogeneity and genetic characteristics of metastatic prostate cancer. Our study confirmed the high intratumoral genetic heterogeneity of prostate cancer in many aspects, including number of shared variants, tumor mutation burden (TMB), variant genes, CNV burden, weighted genome instability index (wGII), CNV profiles, clonal evolutionary process, variant spectrum and mutational signatures. Moreover, we identified several common genetic characteristics of prostate cancer. Alterations of DNA damage repair genes, RTK/RAS pathway associated gene RASGRF1 and autophagy gene EPG5 may be involved in tumorigenesis in prostate cancer. CNV burden and DNA damage repair (DDR) genes may be associated with metastasis of prostate cancer.
前列腺癌是一种异质性疾病，通常无法进行最佳的基因靶向治疗。我们旨在确定前列腺癌的肿瘤内基因组异质性，并探索靶向治疗的候选基因。对 16 名前列腺癌患者的 37 个样本进行了外显子组测序。利用体细胞变异分析、拷贝数变异（CNV）分析、克隆进化分析和变异谱分析，研究转移性前列腺癌的肿瘤内基因组异质性和遗传特征。我们的研究从多个方面证实了前列腺癌的肿瘤内遗传异质性很高，包括共享变异数量、肿瘤突变负担（TMB）、变异基因、CNV 负担、加权基因组不稳定性指数（wGII）、CNV 谱、克隆进化过程、变异谱和突变特征。此外，我们还确定了前列腺癌的一些共同遗传特征。DNA 损伤修复基因、RTK/RAS 通路相关基因 RASGRF1 和自噬基因 EPG5 的改变可能参与了前列腺癌的发生。CNV 负担和 DNA 损伤修复（DDR）基因可能与前列腺癌的转移有关。
