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Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance
PURPOSE: To investigate germline and somatic mutation profiles in Korean patients with prostate cancer using liquid biopsy and solid tissue testing and to evaluate the prognostic value of circulating tumor DNA (ctDNA) in predicting castration resistance in patients with metastatic hormone-sensitive...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Urological Association
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940855/ https://www.ncbi.nlm.nih.gov/pubmed/33660451 http://dx.doi.org/10.4111/icu.20200406 |
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author | Yu, Jiwoong Cho, Eunhae Choi, Joongwon Lim, Joung Eun Lee, Junnam Kang, Minyong Sung, Hyun Hwan Jeong, Byong Chang Seo, Seong Il Jeon, Seong Soo Lee, Hyun Moo Jeon, Hwang Gyun |
author_facet | Yu, Jiwoong Cho, Eunhae Choi, Joongwon Lim, Joung Eun Lee, Junnam Kang, Minyong Sung, Hyun Hwan Jeong, Byong Chang Seo, Seong Il Jeon, Seong Soo Lee, Hyun Moo Jeon, Hwang Gyun |
author_sort | Yu, Jiwoong |
collection | PubMed |
description | PURPOSE: To investigate germline and somatic mutation profiles in Korean patients with prostate cancer using liquid biopsy and solid tissue testing and to evaluate the prognostic value of circulating tumor DNA (ctDNA) in predicting castration resistance in patients with metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: Plasma samples from 56 prostate cancer patients were subjected to next-generation sequencing (NGS) to identify germline mutations and ctDNA analysis using liquid biopsy to detect somatic mutations. Additionally, paired solid cancer tissues from 18 patients were subject to NGS to detect somatic mutations. The clinical parameters and ctDNA profiles of patients with mHSPC were analyzed to evaluate the prognostic value of ctDNA mutations with respect to predicting castration resistance using Cox proportional hazards regression analysis. RESULTS: Germline mutations occurred in 3.6% of the patients in this cohort, with mutations identified in RAD50 (1.8%) and BRCA1 (1.8%). Somatic mutations detected by liquid biopsy and solid tissue testing were common in TP53 (12.5%), PIK3CA (3.6%), and TMPRSS2-ERG (3.6%). Of the 18 patients with paired tissue testing, two patients had at least one identical somatic mutation in both the liquid biopsy and solid tissue testing. In patients with mHSPC, the presence of ctDNA mutations could independently predict the castration resistance development (hazard ratio, 13.048; 95% confidential interval, 1.109–153.505; p=0.041). CONCLUSIONS: Korean patients with prostate cancer showed a relatively low germline mutation rate compared to other ethnicities. The ctDNA mutations detected by liquid biopsy can predict the development of castration resistance in patients with mHSPC. |
format | Online Article Text |
id | pubmed-7940855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Korean Urological Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-79408552021-03-15 Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance Yu, Jiwoong Cho, Eunhae Choi, Joongwon Lim, Joung Eun Lee, Junnam Kang, Minyong Sung, Hyun Hwan Jeong, Byong Chang Seo, Seong Il Jeon, Seong Soo Lee, Hyun Moo Jeon, Hwang Gyun Investig Clin Urol Original Article PURPOSE: To investigate germline and somatic mutation profiles in Korean patients with prostate cancer using liquid biopsy and solid tissue testing and to evaluate the prognostic value of circulating tumor DNA (ctDNA) in predicting castration resistance in patients with metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: Plasma samples from 56 prostate cancer patients were subjected to next-generation sequencing (NGS) to identify germline mutations and ctDNA analysis using liquid biopsy to detect somatic mutations. Additionally, paired solid cancer tissues from 18 patients were subject to NGS to detect somatic mutations. The clinical parameters and ctDNA profiles of patients with mHSPC were analyzed to evaluate the prognostic value of ctDNA mutations with respect to predicting castration resistance using Cox proportional hazards regression analysis. RESULTS: Germline mutations occurred in 3.6% of the patients in this cohort, with mutations identified in RAD50 (1.8%) and BRCA1 (1.8%). Somatic mutations detected by liquid biopsy and solid tissue testing were common in TP53 (12.5%), PIK3CA (3.6%), and TMPRSS2-ERG (3.6%). Of the 18 patients with paired tissue testing, two patients had at least one identical somatic mutation in both the liquid biopsy and solid tissue testing. In patients with mHSPC, the presence of ctDNA mutations could independently predict the castration resistance development (hazard ratio, 13.048; 95% confidential interval, 1.109–153.505; p=0.041). CONCLUSIONS: Korean patients with prostate cancer showed a relatively low germline mutation rate compared to other ethnicities. The ctDNA mutations detected by liquid biopsy can predict the development of castration resistance in patients with mHSPC. The Korean Urological Association 2021-03 2021-01-20 /pmc/articles/PMC7940855/ /pubmed/33660451 http://dx.doi.org/10.4111/icu.20200406 Text en © The Korean Urological Association, 2021 http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Yu, Jiwoong Cho, Eunhae Choi, Joongwon Lim, Joung Eun Lee, Junnam Kang, Minyong Sung, Hyun Hwan Jeong, Byong Chang Seo, Seong Il Jeon, Seong Soo Lee, Hyun Moo Jeon, Hwang Gyun Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance |
title | Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance |
title_full | Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance |
title_fullStr | Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance |
title_full_unstemmed | Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance |
title_short | Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance |
title_sort | genomic mutation profiling using liquid biopsy in korean patients with prostate cancer: circulating tumor dna mutation predicts the development of castration resistance |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940855/ https://www.ncbi.nlm.nih.gov/pubmed/33660451 http://dx.doi.org/10.4111/icu.20200406 |
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