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Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells
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Antal upphovsmän: 112016 (Engelska)Ingår i: SpringerPlus, E-ISSN 2193-1801, Vol. 5, artikel-id 1861Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

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2016. Vol. 5, artikel-id 1861
Nyckelord [en]
Docetaxel resistance, Prostate cancer, RNAseq, Gene fusion, Mutation, Altered expression
Nationell ämneskategori
Biologiska vetenskaper Cancer och onkologi
Identifikatorer
URN: urn:nbn:se:su:diva-137516DOI: 10.1186/s40064-016-3543-0ISI: 000390007800001PubMedID: 27822437OAI: oai:DiVA.org:su-137516DiVA, id: diva2:1066458
Tillgänglig från: 2017-01-18 Skapad: 2017-01-09 Senast uppdaterad: 2023-06-13Bibliografiskt granskad

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Huss, Mikael

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Huss, Mikael
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Institutionen för biokemi och biofysikScience for Life Laboratory (SciLifeLab)
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SpringerPlus
Biologiska vetenskaperCancer och onkologi

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