Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells

Abstract

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 materialThe online version of this article (doi:10.1186/s40064-016-3543-0) contains supplementary material, which is available to authorized users.

Multinucleated polyploidy drives resistance to Docetaxel chemotherapy in prostate cancer

“…It is also likely to be that CDPCs have altered expression of drug transporter proteins, thus making them less susceptible to docetaxel toxicity. ( Aberuyi et al , 2014 ; Rahgozar et al , 2014 ; de Morree et al , 2016 ; Ma et al , 2016 )…”

Characterization of glycine‐N‐acyltransferase like 1 (GLYATL1) in prostate cancer

“…To evaluate the potential role of GLYATL1 in prostate cancer, we analyzed its expression in prostate cancer cell lines. In their study on next‐generation RNAseq in castration‐resistant prostate cancer cell lines, Ma et al found GLYATL1 among the top 8 downregulated genes in PC3 and DU145 (which represent acquired resistance to androgens) vs LNCaP cells. In line with that, we found GLYATL1 to be present in prostate cancer cell lines that express AR (LNCaP, C4‐2B, VCaP, and 22Rv1) and absent in DU145, PC3, benign prostate epithelial cells and RWPE‐1.…”

Mutations, Differential Gene Expression, and Chimeric Transcripts in Esophageal Squamous Cell Carcinoma Show High Heterogeneity

“…Although mutational analysis of transcripts is restricted following removal of InDel mutations and A:T>G:C conversions largely produced by RNA editing [16], all other mutations in coding regions can be successfully analyzed, as was the case in liver and prostate cancer [23], [24].…”

“…RNA-seq is a high-throughput procedure that provides extensive data on genomic alterations with numerous advantages over hybridization-based transcriptome analysis, like detection of rare and alternative transcripts, splice variants, mutations, and quantification of transcript expression [22] . Although mutational analysis of transcripts is restricted following removal of InDel mutations and A:T>G:C conversions largely produced by RNA editing [16] , all other mutations in coding regions can be successfully analyzed, as was the case in liver and prostate cancer [23] , [24] .…”