Homologous recombination repair gene mutations in Chinese localized and locally advanced prostate cancer patients. 2021

Xingran Jiang, and Xiumei Hu, and Yajuan Gu, and Yunlong Li, and Mulan Jin, and Hongying Zhao, and Ruixia Gao, and Zhan Huang, and Jun Lu
Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China. Electronic address: jiang.xingran@foxmail.com.

BACKGROUND Homologous recombination repair gene (HRR) mutations have been proven to be effective biomarkers for PARP inhibitor therapy for metastatic castration resistant prostate cancer. However, the frequency of HRR mutations in patients with localized and locally advanced prostate cancer is still unclear. This study investigated the profile of HRR gene mutations in Chinese localized and locally advanced prostate cancer patients. METHODS 74 patients with localized and locally advanced prostate cancer patients in Beijing Chaoyang Hospital between May 2018 and September 2019 were retrospectively included. Matched prostate cancer and histologically normal tissues were subjected to next-generation sequencing. Pathogenic alterations of 19 HRR genes were examined. RESULTS Ten deleterious and suspected deleterious mutations (4 germline and 6 somatic mutations) were detected in 9 of 74 (12.16 %) patients, occurred in seven HRR-related genes, including CDK12, NBN, ATM, ATR, BRCA2, PALB2 and RAD51C. The mutation frequency of HRR genes in this study (12.16 %) was higher than TCGA cohort (7.29 %), and the mutation sites in 7 HRR genes detected in this cohort were different from those of TCGA data. Patients with HRR gene mutations had higher Gleason grade (≥ 3) (P = 0.03) and risk level (very-high) (P = 0.03). Postoperative prostate specific antigen level and positive surgical margin rate was not associated with HRR gene mutation status. CONCLUSIONS This study illustrated the mutation patterns of HRR genes in Chinese population with localized and locally advanced prostate cancer. These results provide further evidence that HRR gene mutations were more prevalent in patients with higher Gleason grade, or with very-high-risk level. Patients with these clinicopathologic characteristics may need more precise stratification through molecular detection.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D011468 Prostatectomy Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (TRANSURETHRAL RESECTION OF PROSTATE). Prostatectomy, Retropubic,Prostatectomy, Suprapubic,Prostatectomies,Prostatectomies, Retropubic,Prostatectomies, Suprapubic,Retropubic Prostatectomies,Retropubic Prostatectomy,Suprapubic Prostatectomies,Suprapubic Prostatectomy
D011471 Prostatic Neoplasms Tumors or cancer of the PROSTATE. Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D002681 China A country spanning from central Asia to the Pacific Ocean. Inner Mongolia,Manchuria,People's Republic of China,Sinkiang,Mainland China
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old
D012189 Retrospective Studies Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. Retrospective Study,Studies, Retrospective,Study, Retrospective

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