Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate

Objectives To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC‐P). Patients and Methods We performed targeted sequencing of plasma cell‐free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC‐P and 84...

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Published in:BJU international 2022-03, Vol.129 (3), p.345-355
Main Authors: Zhao, Jinge, Sun, Guangxi, Zhu, Sha, Dai, Jindong, Chen, Junru, Zhang, Mengni, Ni, Yuchao, Zhang, Haoran, Shen, Pengfei, Zhao, Xiaochen, Zhang, Bei, Pan, Xiuyi, Nie, Ling, Yin, Xiaoxue, Liang, Jiayu, Zhang, Xingming, Wang, Zhipeng, Zhu, Xudong, Liao, Banghua, Liu, Zhenhua, Armstrong, Cameron M., Gao, Allen C., Huang, Haojie, Chen, Ni, Zeng, Hao
Format: Article
Language:English
Subjects:
Adenocarcinoma
Androgen receptors
BRCA2 protein
Breast cancer
Carcinoma, Intraductal, Noninfiltrating - genetics
Carcinoma, Intraductal, Noninfiltrating - pathology
Castration
Circulating Tumor DNA - genetics
Deoxyribonucleic acid
DNA
DNA repair
DNA sequencing
DNA‐damage repair
Genomics
Humans
Intraductal carcinoma of the prostate
Liquid biopsy
Male
Mutation
NCOR2
p53 Protein
Patients
Phenotype
Phenotypes
Prostate
Prostate - pathology
Prostate cancer
Prostatic Neoplasms - pathology
TP53
Tumors
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Summary:Objectives To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC‐P). Patients and Methods We performed targeted sequencing of plasma cell‐free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC‐P and 84 without IDC‐P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients’ survival outcomes was also explored. Results We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC‐P harboured genomic alterations in DNA repair pathways, respectively (P = 0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC‐P carriers compared to IDC‐P non‐carriers (11.8% [19/161] vs 2.4% [two of 84], P = 0.024). Germline BReast CAncer type 2 susceptibility protein (BRCA2) and somatic cyclin‐dependent kinase 12 (CDK12) defects were specifically identified in IDC‐P carriers relative to PAC (BRCA2: 8.7% [14/161] vs 0% and CDK12: 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC‐P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 (NCOR2) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P = 0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC‐P proportion of ≥10% vs those with an IDC‐P proportion of
ISSN:1464-4096
1464-410X
DOI:10.1111/bju.15530