Prostate cancer(PCa)exhibits epidemiological and molecular heterogeneity.Despite extensive studies of its phenotypic and genetic properties in Western populations,its molecular basis is not clear in Chinese patients.T...Prostate cancer(PCa)exhibits epidemiological and molecular heterogeneity.Despite extensive studies of its phenotypic and genetic properties in Western populations,its molecular basis is not clear in Chinese patients.To determine critical molecular characteristics and explore correlations between genomic markers and clinical parameters in Chinese populations,we applied an integrative genetic/transcriptomic assay that combines targeted next-generation sequencing and quantitative real-time PCR(qRT-PCR)on samples from 46 Chinese patients with PCa.Lysine(K)-specific methyltransferase 2D(KMT2D),zinc finger homeobox 3(ZFHX3),A-kinase anchoring protein 9(AKAP9),and GLI family zinc finger 1(GLI1)were frequently mutated in our cohort.Moreover,a clinicopathological analysis showed that RB transcriptional corepressor 1(RB1)deletion was common in patients with a high risk of disease progression.Remarkably,four genomic events,MYC proto-oncogene(MYC)amplification,RB1 deletion,APC regulator of WNT signaling pathway(APC)mutation or deletion,and cyclin-dependent kinase 12(CDK12)mutation,were correlated with poor disease-free survival.In addition,a close link between KMT2D expression and the androgen receptor(AR)signaling pathway was observed both in our cohort and in The Cancer Genome Atlas Prostate Adenocarcinoma(TCGA-PRAD)data.In summary,our results demonstrate the feasibility and benefits of integrative molecular characterization of PCa samples in disease pathology research and personalized medicine.展开更多
基金This work was mainly supported by the National Key R&D Program of China(No.2017YFC1103403)the National Natural Science Foundation of China(No.21773199,No.61427807 and No.81872092)+1 种基金the Sanming Project of Medicine in Shenzhen(No.SZSM201612019)the PhD Start-up Fund of Natural Science Foundation of Guangdong Province of China(No.2016A030310287).
文摘Prostate cancer(PCa)exhibits epidemiological and molecular heterogeneity.Despite extensive studies of its phenotypic and genetic properties in Western populations,its molecular basis is not clear in Chinese patients.To determine critical molecular characteristics and explore correlations between genomic markers and clinical parameters in Chinese populations,we applied an integrative genetic/transcriptomic assay that combines targeted next-generation sequencing and quantitative real-time PCR(qRT-PCR)on samples from 46 Chinese patients with PCa.Lysine(K)-specific methyltransferase 2D(KMT2D),zinc finger homeobox 3(ZFHX3),A-kinase anchoring protein 9(AKAP9),and GLI family zinc finger 1(GLI1)were frequently mutated in our cohort.Moreover,a clinicopathological analysis showed that RB transcriptional corepressor 1(RB1)deletion was common in patients with a high risk of disease progression.Remarkably,four genomic events,MYC proto-oncogene(MYC)amplification,RB1 deletion,APC regulator of WNT signaling pathway(APC)mutation or deletion,and cyclin-dependent kinase 12(CDK12)mutation,were correlated with poor disease-free survival.In addition,a close link between KMT2D expression and the androgen receptor(AR)signaling pathway was observed both in our cohort and in The Cancer Genome Atlas Prostate Adenocarcinoma(TCGA-PRAD)data.In summary,our results demonstrate the feasibility and benefits of integrative molecular characterization of PCa samples in disease pathology research and personalized medicine.
