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A genetic map of the chromatin regulators to drug response in cancer cells
BACKGROUND: Diverse drug vulnerabilities owing to the Chromatin regulators (CRs) genetic interaction across various cancers, but the identification of CRs genetic interaction remains challenging. METHODS: In order to provide a global view of the CRs genetic interaction in cancer cells, we developed...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9523919/ https://www.ncbi.nlm.nih.gov/pubmed/36180906 http://dx.doi.org/10.1186/s12967-022-03651-w |
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author | Chen, Bo Li, Pengfei Liu, Mingyue Liu, Kaidong Zou, Min Geng, Yiding Zhuang, Shuping Xu, Huanhuan Wang, Linzhu Chen, Tingting Li, Yawei Zhao, Zhangxiang Qi, Lishuang Gu, Yunyan |
author_facet | Chen, Bo Li, Pengfei Liu, Mingyue Liu, Kaidong Zou, Min Geng, Yiding Zhuang, Shuping Xu, Huanhuan Wang, Linzhu Chen, Tingting Li, Yawei Zhao, Zhangxiang Qi, Lishuang Gu, Yunyan |
author_sort | Chen, Bo |
collection | PubMed |
description | BACKGROUND: Diverse drug vulnerabilities owing to the Chromatin regulators (CRs) genetic interaction across various cancers, but the identification of CRs genetic interaction remains challenging. METHODS: In order to provide a global view of the CRs genetic interaction in cancer cells, we developed a method to identify potential drug response-related CRs genetic interactions for specific cancer types by integrating the screen of CRISPR-Cas9 and pharmacogenomic response datasets. RESULTS: Totally, 625 drug response-related CRs synthetic lethality (CSL) interactions and 288 CRs synthetic viability (CSV) interactions were detected. Systematically network analysis presented CRs genetic interactions have biological function relationship. Furthermore, we validated CRs genetic interactions induce multiple omics deregulation in The Cancer Genome Atlas. We revealed the colon adenocarcinoma patients (COAD) with mutations of a CRs set (EP300, MSH6, NSD2 and TRRAP) mediate a better survival with low expression of MAP2 and could benefit from taxnes. While the COAD patients carrying at least one of the CSV interactions in Vorinostat CSV module confer a poor prognosis and may be resistant to Vorinostat treatment. CONCLUSIONS: The CRs genetic interaction map provides a rich resource to investigate cancer-associated CRs genetic interaction and proposes a powerful strategy of biomarker discovery to guide the rational use of agents in cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03651-w. |
format | Online Article Text |
id | pubmed-9523919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-95239192022-10-01 A genetic map of the chromatin regulators to drug response in cancer cells Chen, Bo Li, Pengfei Liu, Mingyue Liu, Kaidong Zou, Min Geng, Yiding Zhuang, Shuping Xu, Huanhuan Wang, Linzhu Chen, Tingting Li, Yawei Zhao, Zhangxiang Qi, Lishuang Gu, Yunyan J Transl Med Research BACKGROUND: Diverse drug vulnerabilities owing to the Chromatin regulators (CRs) genetic interaction across various cancers, but the identification of CRs genetic interaction remains challenging. METHODS: In order to provide a global view of the CRs genetic interaction in cancer cells, we developed a method to identify potential drug response-related CRs genetic interactions for specific cancer types by integrating the screen of CRISPR-Cas9 and pharmacogenomic response datasets. RESULTS: Totally, 625 drug response-related CRs synthetic lethality (CSL) interactions and 288 CRs synthetic viability (CSV) interactions were detected. Systematically network analysis presented CRs genetic interactions have biological function relationship. Furthermore, we validated CRs genetic interactions induce multiple omics deregulation in The Cancer Genome Atlas. We revealed the colon adenocarcinoma patients (COAD) with mutations of a CRs set (EP300, MSH6, NSD2 and TRRAP) mediate a better survival with low expression of MAP2 and could benefit from taxnes. While the COAD patients carrying at least one of the CSV interactions in Vorinostat CSV module confer a poor prognosis and may be resistant to Vorinostat treatment. CONCLUSIONS: The CRs genetic interaction map provides a rich resource to investigate cancer-associated CRs genetic interaction and proposes a powerful strategy of biomarker discovery to guide the rational use of agents in cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03651-w. BioMed Central 2022-09-30 /pmc/articles/PMC9523919/ /pubmed/36180906 http://dx.doi.org/10.1186/s12967-022-03651-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chen, Bo Li, Pengfei Liu, Mingyue Liu, Kaidong Zou, Min Geng, Yiding Zhuang, Shuping Xu, Huanhuan Wang, Linzhu Chen, Tingting Li, Yawei Zhao, Zhangxiang Qi, Lishuang Gu, Yunyan A genetic map of the chromatin regulators to drug response in cancer cells |
title | A genetic map of the chromatin regulators to drug response in cancer cells |
title_full | A genetic map of the chromatin regulators to drug response in cancer cells |
title_fullStr | A genetic map of the chromatin regulators to drug response in cancer cells |
title_full_unstemmed | A genetic map of the chromatin regulators to drug response in cancer cells |
title_short | A genetic map of the chromatin regulators to drug response in cancer cells |
title_sort | genetic map of the chromatin regulators to drug response in cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9523919/ https://www.ncbi.nlm.nih.gov/pubmed/36180906 http://dx.doi.org/10.1186/s12967-022-03651-w |
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