Comparative Analysis of Genomic Alterations across Castration Sensitive and Castration Resistant Prostate Cancer via Circulating Tumor DNA Sequencing

No AccessJournal of UrologyAdult Urology1 Feb 2021Comparative Analysis of Genomic Alterations across Castration Sensitive and Castration Resistant Prostate Cancer via Circulating Tumor DNA Sequencing Liancheng Fan, Xiaochen Fei, Yinjie Zhu, Jiahua Pan, Jianjun Sha, Chenfei Chi, Yiming Gong, Xinxing Du, Lixin Zhou, Baijun Dong, and Wei Xue Liancheng FanLiancheng Fan Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , Xiaochen FeiXiaochen Fei Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , Yinjie ZhuYinjie Zhu Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , Jiahua PanJiahua Pan Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , Jianjun ShaJianjun Sha Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , Chenfei ChiChenfei Chi Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , Yiming GongYiming Gong Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , Xinxing DuXinxing Du Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , Lixin ZhouLixin Zhou Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , Baijun DongBaijun Dong ‡Correspondence: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, China telephone: +86 21 68383757; E-mail Address: [email protected] [BD]; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China , and Wei XueWei Xue ‡ E-mail Address: [email protected] [WX]). Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China View All Author Informationhttps://doi.org/10.1097/JU.0000000000001363AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: To explore the genomic profiles of Chinese patients with castration sensitive prostate cancer and those with metastatic castration resistant prostate cancer via germline and circulating tumor DNA sequencing. Materials and Methods: A hybridization capture based next-generation sequencing assay was used to identify germline and somatic alterations in 50 genes including androgen receptor pathway genes, DNA damage repair pathway genes, TP53 and RB1. Results: We successfully sequenced DNA from 396 blood samples and 32 matched tumor tissue samples from 396 patients. We observed a similar frequency of deleterious germline alterations between patients with castration sensitive prostate cancer and metastatic castration resistant prostate cancer (8.9% vs 9.8%, p >0.05). There was a high consistency (90.9%) between metastatic tumor tissue and matched circulating tumor DNA. Among patients who were circulating tumor DNA positive we observed significantly higher alteration frequencies of CDK12 (27.2% vs 6.4%, p <0.001) and FOXA1 (36.8% vs 15.3%, p <0.001) in our metastatic castration resistant prostate cancer cohort compared with the SU2C-PCF (Stand Up to Cancer-Prostate Cancer Foundation) cohort. Alteration frequencies of DNA damage repair pathway genes (66.7% vs 41.5%, p=0.015) and androgen receptor pathway genes (71.9% vs 48.8%, p=0.018) in patients with metastatic castration resistant prostate cancer were higher than in patients with de novo metastatic castration sensitive prostate cancer. Androgen receptor alteration was selectively enriched in metastatic castration resistant prostate cancer. Conclusions: Through genomic profiling of prostate cancer across clinical states we identified a similar frequency of deleterious germline alterations between patients with castration sensitive prostate cancer and metastatic castration resistant prostate cancer. We explored the genomic diversity of androgen receptor and DNA damage repair pathway genes between patients with metastatic castration sensitive prostate cancer and metastatic castration resistant prostate cancer. Higher alteration frequencies of CDK12 and FOXA1 were observed in our metastatic castration resistant prostate cancer cohort than in the SU2C-PCF cohort. Our findings support the view that circulating tumor DNA sequencing could guide clinical treatment for metastatic prostate cancer. References 1. : Integrative clinical genomics of advanced prostate cancer. Cell 2015; 161: 1215. 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Google Scholar Supported by National Natural Science Foundation of China (81572536, 81672850, 81772742, 81702840, 81702542, 81972578, 81902863 and 82002710), Science and Technology Commission of Shanghai Municipality (19411967400, 19ZR1431000, 19XD1402300, 19YF1428400), Shanghai Municipal Health Commission (201640247, 2019LJ11), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20152215, 20191906), Shanghai Jiao Tong University (YG2016ZD08, YG2017MS47, YG2017MS52); Innovation Fund for Translational Research of Shanghai Jiao Tong University School of Medicine (TM201907), Shanghai Sailing Program (20YF1425300) and Incubating Program for clinical Research and Innovation of Renji Hospital Shanghai Jiao Tong University School of Medicine (PYZY 16-008, PYXJS16-015, RJZZ19-17). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited ByFan L, Fei X, Zhu Y, Chi C, Pan J, Sha J, Xin Z, Gong Y, Du X, Wang Y, Dong B and Xue W (2021) Distinct Response to Platinum-Based Chemotherapy among Patients with Metastatic Castration-Resistant Prostate Cancer Harboring Alterations in Genes Involved in Homologous RecombinationJournal of Urology, VOL. 206, NO. 3, (630-637), Online publication date: 1-Sep-2021. Volume 205Issue 2February 2021Page: 461-469Supplementary Materials Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.Keywordsprostatic neoplasmsreceptors, androgensDNA repaircyclin-dependent kinasescirculating tumor DNAAcknowledgmentsTingting Zhao, Xuan Zou and Yining Yang gave strong support to this study.MetricsAuthor Information Liancheng Fan Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author Xiaochen Fei Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author Yinjie Zhu Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author Jiahua Pan Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Jianjun Sha Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Chenfei Chi Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Yiming Gong Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Xinxing Du Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Lixin Zhou Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Baijun Dong Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ‡Correspondence: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, China telephone: +86 21 68383757; E-mail Address: [email protected] [BD]; Equal study contribution. More articles by this author Wei Xue Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ‡ E-mail Address: [email protected] [WX]). Equal study contribution. More articles by this author Expand All Supported by National Natural Science Foundation of China (81572536, 81672850, 81772742, 81702840, 81702542, 81972578, 81902863 and 82002710), Science and Technology Commission of Shanghai Municipality (19411967400, 19ZR1431000, 19XD1402300, 19YF1428400), Shanghai Municipal Health Commission (201640247, 2019LJ11), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20152215, 20191906), Shanghai Jiao Tong University (YG2016ZD08, YG2017MS47, YG2017MS52); Innovation Fund for Translational Research of Shanghai Jiao Tong University School of Medicine (TM201907), Shanghai Sailing Program (20YF1425300) and Incubating Program for clinical Research and Innovation of Renji Hospital Shanghai Jiao Tong University School of Medicine (PYZY 16-008, PYXJS16-015, RJZZ19-17). Advertisement PDF DownloadLoading ...