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Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells
Docetaxel has been the standard first-line therapy in metastatic castration resistant prostate cancer. The survival benefit is, however, limited by either primary or acquired resistance. In this study, Du145 prostate cancer cells were converted to docetaxel-resistant cells Du145-R and Du145-RB by in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078122/ https://www.ncbi.nlm.nih.gov/pubmed/27822437 http://dx.doi.org/10.1186/s40064-016-3543-0 |
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author | Ma, Yuanjun Miao, Yali Peng, Zhuochun Sandgren, Johanna De Ståhl, Teresita Díaz Huss, Mikael Lennartsson, Lena Liu, Yanling Nistér, Monica Nilsson, Sten Li, Chunde |
author_facet | Ma, Yuanjun Miao, Yali Peng, Zhuochun Sandgren, Johanna De Ståhl, Teresita Díaz Huss, Mikael Lennartsson, Lena Liu, Yanling Nistér, Monica Nilsson, Sten Li, Chunde |
author_sort | Ma, Yuanjun |
collection | PubMed |
description | Docetaxel has been the standard first-line therapy in metastatic castration resistant prostate cancer. The survival benefit is, however, limited by either primary or acquired resistance. In this study, Du145 prostate cancer cells were converted to docetaxel-resistant cells Du145-R and Du145-RB by in vitro culturing. Next generation RNAseq was employed to analyze these cell lines. Forty-two genes were identified to have acquired mutations after the resistance development, of which thirty-four were found to have mutations in published sequencing studies using prostate cancer samples from patients. Fourteen novel and 2 previously known fusion genes were inferred from the RNA-seq data, and 13 of these were validated by RT-PCR and/or re-sequencing. Four in-frame fusion transcripts could be transcribed into fusion proteins in stably transfected HEK293 cells, including MYH9-EIF3D and LDLR-RPL31P11, which were specific identified or up-regulated in the docetaxel resistant DU145 cells. A panel of 615 gene transcripts was identified to have significantly changed expression profile in the docetaxel resistant cells. These transcriptional changes have potential for further study as predictive biomarkers and as targets of docetaxel treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-3543-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5078122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-50781222016-11-07 Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells Ma, Yuanjun Miao, Yali Peng, Zhuochun Sandgren, Johanna De Ståhl, Teresita Díaz Huss, Mikael Lennartsson, Lena Liu, Yanling Nistér, Monica Nilsson, Sten Li, Chunde Springerplus Research Docetaxel has been the standard first-line therapy in metastatic castration resistant prostate cancer. The survival benefit is, however, limited by either primary or acquired resistance. In this study, Du145 prostate cancer cells were converted to docetaxel-resistant cells Du145-R and Du145-RB by in vitro culturing. Next generation RNAseq was employed to analyze these cell lines. Forty-two genes were identified to have acquired mutations after the resistance development, of which thirty-four were found to have mutations in published sequencing studies using prostate cancer samples from patients. Fourteen novel and 2 previously known fusion genes were inferred from the RNA-seq data, and 13 of these were validated by RT-PCR and/or re-sequencing. Four in-frame fusion transcripts could be transcribed into fusion proteins in stably transfected HEK293 cells, including MYH9-EIF3D and LDLR-RPL31P11, which were specific identified or up-regulated in the docetaxel resistant DU145 cells. A panel of 615 gene transcripts was identified to have significantly changed expression profile in the docetaxel resistant cells. These transcriptional changes have potential for further study as predictive biomarkers and as targets of docetaxel treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-3543-0) contains supplementary material, which is available to authorized users. Springer International Publishing 2016-10-24 /pmc/articles/PMC5078122/ /pubmed/27822437 http://dx.doi.org/10.1186/s40064-016-3543-0 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Ma, Yuanjun Miao, Yali Peng, Zhuochun Sandgren, Johanna De Ståhl, Teresita Díaz Huss, Mikael Lennartsson, Lena Liu, Yanling Nistér, Monica Nilsson, Sten Li, Chunde Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells |
title | Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells |
title_full | Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells |
title_fullStr | Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells |
title_full_unstemmed | Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells |
title_short | Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells |
title_sort | identification of mutations, gene expression changes and fusion transcripts by whole transcriptome rnaseq in docetaxel resistant prostate cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078122/ https://www.ncbi.nlm.nih.gov/pubmed/27822437 http://dx.doi.org/10.1186/s40064-016-3543-0 |
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