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Integrative sequencing reveals alterations in untreated and castration resistant prostate cancer

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.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001000609 Illumina HiSeq 2000 53
EGAD00001000610 Illumina HiSeq 2000 51
EGAD00001000611 Illumina HiSeq 2000 43
EGAD00001000612 Illumina HiSeq 2000 40
EGAD00001007921 Illumina NovaSeq 6000 2
Publications Citations
Recurrent SKIL-activating rearrangements in ETS-negative prostate cancer.
Oncotarget 6: 2015 6235-6250
Integrative proteomics in prostate cancer uncovers robustness against genomic and transcriptomic aberrations during disease progression.
Nat Commun 9: 2018 1176
Gene Regulation Network Analysis on Human Prostate Orthografts Highlights a Potential Role for the JMJD6 Regulon in Clinical Prostate Cancer.
Cancers (Basel) 13: 2021 2094
Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse.
Nat Commun 12: 2021 5307
Spatial transcriptomics technology in cancer research.
Front Oncol 12: 2022 1019111
Identification of long noncoding RNAs with aberrant expression in prostate cancer metastases.
Endocr Relat Cancer 30: 2023 e220247