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Identification of m...
Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells
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- Ma, Yuanjun (author)
- Karolinska Institutet
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Miao, Yali (author)
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- Peng, Zhuochun (author)
- Karolinska Institutet
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- Sandgren, Johanna (author)
- Karolinska Institutet
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- De Stahl, Teresita Diaz (author)
- Karolinska Institutet
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- Huss, Mikael (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)
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Lennartsson, Lena (author)
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Liu, Yanling (author)
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- Nister, Monica (author)
- Karolinska Institutet
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- Nilsson, Sten (author)
- Karolinska Institutet
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- Li, Chunde (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2016-10-24
- 2016
- English.
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In: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 5
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Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Docetaxel resistance
- Prostate cancer
- RNAseq
- Gene fusion
- Mutation
- Altered expression
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ma, Yuanjun
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Miao, Yali
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Peng, Zhuochun
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Sandgren, Johann ...
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De Stahl, Teresi ...
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Huss, Mikael
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show more...
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Lennartsson, Len ...
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Liu, Yanling
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Nister, Monica
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Nilsson, Sten
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Li, Chunde
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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SpringerPlus
- By the university
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Stockholm University
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Karolinska Institutet