Study

Integrative sequencing reveals alterations in untreated and castration resistant prostate cancer

Study ID Alternative Stable ID Type
EGAS00001000526 Other

Study Description

We report the integrative sequencing of genomic, transcriptomic and DNA methylation changes in 28 untreated (PC) and 13 castration resistant prostate cancers (CRPC). AR, TGF-β and WNT signaling pathways were altered in CRPCs. We identified two new fusion genes, TMPRSS2-SKIL and DOT1L-HES6. Fusion analysis in an independent cohort validated SKIL as a recurrent 3’ fusion partner and oncogene in prostate cancer. The HES6 fusion was found in an AR-negative CRPC, and HES6 overexpression in vitro led to androgen independent growth. A distinct DNA methylation signature was found for CRPC. Transcriptome assembly uncovered 128 previously unannotated prostate cancer associated transcripts, including the ERG regulated transcript TPCAT-10-36067 whose knockdown had a dramatic effect on the growth, invasiveness, and rate of apoptosis of prostate cancer cells.

Study Datasets 4 datasets.

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Dataset ID Description Technology Samples
EGAD00001000609
Whole transcriptome sequencing of 28 untreated prostate cancers, 13 castration resistant prostate cancers, and 12 benign prostatic hyperplasias.
Illumina HiSeq 2000 53
EGAD00001000610
Methylated DNA immunoprecipitation sequencing of 28 untreated prostate cancers, 11 castration resistant prostate cancers, and 12 benign prostatic hyperplasias.
Illumina HiSeq 2000 51
EGAD00001000611
Small RNA sequencing of 28 untreated prostate cancers, 12 castration resistant prostate cancers, and 3 benign prostatic hyperplasias.
Illumina HiSeq 2000 43
EGAD00001000612
Low coverage whole genome sequencing of 27 untreated prostate cancers, 9 castration resistant prostate cancers, and 4 benign prostatic hyperplasias.
Illumina HiSeq 2000 40

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