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Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients

SIMPLE SUMMARY: Somatic and germline aberrations in homologous recombinant repair (HHR) genes are associated with increased incidence and poor prognosis for prostate cancer. Through next-generation sequencing of prostate cancer patients across all clinical states from north China, here the authors i...

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Autores principales: Liu, Yixiao, Jin, Bo, Shen, Cheng, Gao, Xianshu, Qi, Xin, Ma, Mingwei, Li, Hongzhen, Hao, Han, Tang, Qi, Yang, Kaiwei, Mi, Yue, Guan, Jie, Feng, Xuero, He, Zhisong, Li, Haixia, Yu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091863/
https://www.ncbi.nlm.nih.gov/pubmed/37064136
http://dx.doi.org/10.3389/fonc.2023.1086517
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author Liu, Yixiao
Jin, Bo
Shen, Cheng
Gao, Xianshu
Qi, Xin
Ma, Mingwei
Li, Hongzhen
Hao, Han
Tang, Qi
Yang, Kaiwei
Mi, Yue
Guan, Jie
Feng, Xuero
He, Zhisong
Li, Haixia
Yu, Wei
author_facet Liu, Yixiao
Jin, Bo
Shen, Cheng
Gao, Xianshu
Qi, Xin
Ma, Mingwei
Li, Hongzhen
Hao, Han
Tang, Qi
Yang, Kaiwei
Mi, Yue
Guan, Jie
Feng, Xuero
He, Zhisong
Li, Haixia
Yu, Wei
author_sort Liu, Yixiao
collection PubMed
description SIMPLE SUMMARY: Somatic and germline aberrations in homologous recombinant repair (HHR) genes are associated with increased incidence and poor prognosis for prostate cancer. Through next-generation sequencing of prostate cancer patients across all clinical states from north China, here the authors identified a somatic mutational rate of 3% and a germline mutational rate of 3.9% for HRR genes using 200 tumor tissues and 714 blood specimens. Thus, mutational rates in HRR genes were lower compared with previous studies. BACKGROUND: Homologous recombination repair deficiency is associated with higher risk and poorer prognosis for prostate cancer. However, the landscapes of somatic and germline mutations in these genes remain poorly defined in Chinese patients, especially for those with localized disease and those from north part of China. In this study, we explore the genomic profiles of these patients. METHODS: We performed next-generation sequencing with 200 tumor tissues and 714 blood samples from prostate cancer patients at Peking University First Hospital, using a 32 gene panel including 19 homologous recombination repair genes. RESULTS: TP53, PTEN, KRAS were the most common somatic aberrations; BRCA2, NBN, ATM were the most common germline aberrations. In terms of HRR genes, 3% (6/200) patients harbored somatic aberrations, and 3.8% (28/714) patients harbored germline aberrations. 98.0% (196/200) somatic-tested and 72.7% (519/714) germline tested patients underwent prostatectomy, of which 28.6% and 42.0% had Gleason scores ≥8 respectively. Gleason scores at either biopsy or prostatectomy were predictive for somatic aberrations in general and in TP53; while age of onset <60 years old, PSA at diagnosis, and Gleason scores at biopsy were clinical factors associated with positive germline aberrations in BRCA2/ATM. CONCLUSIONS: Our results showed a distinct genomic profile in homologous recombination repair genes for patients with prostate cancer across all clinical states from north China. Clinicians may consider to expand the prostate cancer patients receiving genetic tests to include more individuals due to the weak guiding role by the clinical factors currently available.
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spelling pubmed-100918632023-04-13 Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients Liu, Yixiao Jin, Bo Shen, Cheng Gao, Xianshu Qi, Xin Ma, Mingwei Li, Hongzhen Hao, Han Tang, Qi Yang, Kaiwei Mi, Yue Guan, Jie Feng, Xuero He, Zhisong Li, Haixia Yu, Wei Front Oncol Oncology SIMPLE SUMMARY: Somatic and germline aberrations in homologous recombinant repair (HHR) genes are associated with increased incidence and poor prognosis for prostate cancer. Through next-generation sequencing of prostate cancer patients across all clinical states from north China, here the authors identified a somatic mutational rate of 3% and a germline mutational rate of 3.9% for HRR genes using 200 tumor tissues and 714 blood specimens. Thus, mutational rates in HRR genes were lower compared with previous studies. BACKGROUND: Homologous recombination repair deficiency is associated with higher risk and poorer prognosis for prostate cancer. However, the landscapes of somatic and germline mutations in these genes remain poorly defined in Chinese patients, especially for those with localized disease and those from north part of China. In this study, we explore the genomic profiles of these patients. METHODS: We performed next-generation sequencing with 200 tumor tissues and 714 blood samples from prostate cancer patients at Peking University First Hospital, using a 32 gene panel including 19 homologous recombination repair genes. RESULTS: TP53, PTEN, KRAS were the most common somatic aberrations; BRCA2, NBN, ATM were the most common germline aberrations. In terms of HRR genes, 3% (6/200) patients harbored somatic aberrations, and 3.8% (28/714) patients harbored germline aberrations. 98.0% (196/200) somatic-tested and 72.7% (519/714) germline tested patients underwent prostatectomy, of which 28.6% and 42.0% had Gleason scores ≥8 respectively. Gleason scores at either biopsy or prostatectomy were predictive for somatic aberrations in general and in TP53; while age of onset <60 years old, PSA at diagnosis, and Gleason scores at biopsy were clinical factors associated with positive germline aberrations in BRCA2/ATM. CONCLUSIONS: Our results showed a distinct genomic profile in homologous recombination repair genes for patients with prostate cancer across all clinical states from north China. Clinicians may consider to expand the prostate cancer patients receiving genetic tests to include more individuals due to the weak guiding role by the clinical factors currently available. Frontiers Media S.A. 2023-03-29 /pmc/articles/PMC10091863/ /pubmed/37064136 http://dx.doi.org/10.3389/fonc.2023.1086517 Text en Copyright © 2023 Liu, Jin, Shen, Gao, Qi, Ma, Li, Hao, Tang, Yang, Mi, Guan, Feng, He, Li and Yu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Liu, Yixiao
Jin, Bo
Shen, Cheng
Gao, Xianshu
Qi, Xin
Ma, Mingwei
Li, Hongzhen
Hao, Han
Tang, Qi
Yang, Kaiwei
Mi, Yue
Guan, Jie
Feng, Xuero
He, Zhisong
Li, Haixia
Yu, Wei
Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients
title Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients
title_full Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients
title_fullStr Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients
title_full_unstemmed Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients
title_short Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients
title_sort somatic and germline aberrations in homologous recombination repair genes in chinese prostate cancer patients
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091863/
https://www.ncbi.nlm.nih.gov/pubmed/37064136
http://dx.doi.org/10.3389/fonc.2023.1086517
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