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 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.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Yuanjun
Y
Ma
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden ; Department of Obstetrics and Gynecology, Beijing University People's Hospital, Beijing, China.
Yali
Y
Miao
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Zhuochun
Z
Peng
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Johanna
J
Sandgren
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Teresita Díaz
TD
De Ståhl
SciLifeLab (Science for Life Laboratory), Stockholm, Sweden.
Mikael
M
Huss
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Lena
L
Lennartsson
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Yanling
Y
Liu
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden ; Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, Sweden.
Monica
M
Nistér
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden ; Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden.
Sten
S
Nilsson
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden ; Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden.
Chunde
C
Li
Altered expression; Docetaxel resistance; Gene fusion; Mutation; Prostate cancer; RNAseq