Need Help?

Molecular evolution and clinical trajectories of prostate cancer identifies novel markers for risk stratification

Prostate cancer is a highly heterogeneous disease that is thought to develop over many years. Identifying the earliest somatic changes can give important insights into the tumour evolution and aid in stratifying high- from low-risk diseases. Here we pursued integrative whole-genome, transcriptome and methylome-based analysis of early-onset prostate cancer patients. Characterisation of genomic alterations across 270 PCa tumours revealed age-related genomic alterations and mutation signatures including BRCAness and APOBEC. We used methylation- and expression-data to identify four molecular subgroups, which included a highly aggressive tumour subgroup that frequently involved recurrent duplications and increased expression of ESRP1. Analysis of 12,000 tissue-microarray tumour samples demonstrated that ESRP1 is a candidate biomarker associated with faster proliferation rate and shorter time to relapse. We combine the patterns of molecular co-occurrence, risk-stratification and subgroup information to deconvolute tumor heterogeneity, which reveal complex but recurrent clinical trajectories of prostate cancer.

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
EGAD00001004791 Illumina HiSeq 2000 1
EGAD00001007669 HiSeq X Ten Illumina HiSeq 2000 141
EGAD00001007861 Illumina HiSeq 2000 320
Publications Citations
Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories.
Cancer Cell 34: 2018 996-1011.e8
Direct interaction of β-catenin with nuclear ESM1 supports stemness of metastatic prostate cancer.
EMBO J 40: 2021 e105450
miR-449a Repression Leads to Enhanced NOTCH Signaling in TMPRSS2:ERG Fusion Positive Prostate Cancer Cells.
Cancers (Basel) 13: 2021 964
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
A novel lysosome-related gene signature coupled with gleason score for prognosis prediction in prostate cancer.
Front Genet 14: 2023 1135365
Characterization and evaluation of gene fusions as a measure of genetic instability and disease prognosis in prostate cancer.
BMC Cancer 23: 2023 575