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Intratumoral heterogeneity and genetic characteristics of prostate cancer
Author(s) -
Wu Bo,
Lu Xin,
Shen Haibo,
Yuan Xiaobin,
Wang Xin,
Yin Nan,
Sun Libin,
Shen Pengliang,
Hu Caoyang,
Jiang Huanrong,
Wang Dongwen
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32961
Subject(s) - prostate cancer , chromoplexy , genetic heterogeneity , biology , cancer , exome sequencing , carcinogenesis , somatic evolution in cancer , genome instability , metastasis , copy number variation , prostate , cancer research , mutation , genetics , gene , genome , dna damage , pca3 , phenotype , dna
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.