Publications
2026
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Recovering anaerobic bacterial genomes in saliva, tumour and blood whole genome sequencing data from patients with prostate cancer
Microbial constituents in the gastrointestinal tract, the urine and prostate tissue are being linked with clinical differences in prostate cancer, and a recent meta-analysis has linked periodontal disease to this cancer. Several hypotheses exist regarding how specific bacteria can contribute towards the development of prostate cancer. Recovering microbial genomes, and their genomic features, from clinical samples and investigating fine-scale taxonomy is a critical first step in investigating... -
Androgen receptor drives divergent chromatin accessibility programs in benign and malignant prostate epithelial cells
Androgen receptor (AR) activation alters chromatin structure in prostate cancer (PC) cells, but its impact in nonmalignant prostate epithelial cells (NPEC) remains poorly characterized due to lack of representative models. We leveraged our previously established NPEC (RWPE-1-AR and RWPE-1-Ctrl) and PC (LNCaP-pcDNA3.1 and LNCaP-ARhi) cell models to profile androgen-driven chromatin responses using assay for transposase-accessible chromatin with sequencing (ATAC-seq). In the absence of androgen,... -
Disruption of androgen receptor-cofactor interactions by the RNA-binding protein FUS/TLS alters androgen signalling in prostate cancer
Prostate cancer is dependent upon the androgen receptor (AR), the activity of which is modified by cofactors that either enhance or repress its activity, often in a context-dependent manner. FUS/TLS is a multifunctional protein known to be important in multiple cancer types; in prostate cancer, we previously showed that FUS has a potential tumour suppressor role. Here, transcriptomic analysis of the LNCaP prostate cancer cell line shows a significant overlap in genes regulated by FUS and the...
2025
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Identification of protein-coding genes associated with metastatic prostate cancer
Prostate cancer (PCa) is a significant cause of male mortality worldwide. Since metastases are the underlying cause of lethality, identifying markers for metastatic potential would be highly valuable. To address this issue, we set out to identify protein-coding genes with metastasis-specific expression changes in PCa. We employed a previously reported unique cohort consisting of metastases from castration-resistant prostate cancer (mCRPC) and matching primary tumors. Our comprehensive gene... -
PIONEER big data platform for prostate cancer: lessons for advancing future real-world evidence research
Prostate Cancer Diagnosis and Treatment Enhancement through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer. PIONEER brings together 34 private and public stakeholders from 9 countries in one multidisciplinary research consortium with the aim of positively transforming the field of prostate cancer clinical care by answering pressing questions related to prostate cancer screening, diagnosis and treatment. PIONEER has developed a unique...
2024
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Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer
Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 120 patients.... -
PIONEER big data platform for prostate cancer: lessons for advancing future real-world evidence research
Prostate Cancer Diagnosis and Treatment Enhancement through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer. PIONEER brings together 34 private and public stakeholders from 9 countries in one multidisciplinary research consortium with the aim of positively transforming the field of prostate cancer clinical care by answering pressing questions related to prostate cancer screening, diagnosis and treatment. PIONEER has developed a unique... -
Long noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer
While hundreds of cancer-associated long noncoding RNAs (lncRNAs) have been discovered, their functional role in cancer cells is still largely a mystery. An increasing number of lncRNAs are recognized to function in the cytoplasm, e.g., as modulators of translation. Here, we investigated the detailed molecular identity and functional role of EPCART, a lncRNA we previously discovered to be a potential oncogene in prostate cancer (PCa). First, we interrogated the transcript structure of EPCART and... -
Germline-specific RNA helicase DDX4 forms cytoplasmic granules in cancer cells and promotes tumor growth
Cancer cells undergo major epigenetic alterations and transcriptomic changes, including ectopic expression of tissue- and cell-type-specific genes. Here, we show that the germline-specific RNA helicase DDX4 forms germ-granule-like cytoplasmic ribonucleoprotein granules in various human tumors, but not in cultured cancer cells. These cancerous DDX4 complexes contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells... -
Survivorship Data in Prostate Cancer: Where Are We and Where Do We Need To Be?
Cancer survivorship was recently identified as a prostate cancer (PCa) research priority by PIONEER, a European network of excellence for big data in PCa. Despite being a research priority, cancer survivorship lacks a clear and agreed definition, and there is a distinct paucity of patient-reported outcome (PRO) data available on the subject. Data collection on cancer survivorship depends on the availability and implementation of (validated) routinely collected patient-reported outcome measures...
2023
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Survivorship Data in Prostate Cancer: Where Are We and Where Do We Need To Be?
Cancer survivorship was recently identified as a prostate cancer (PCa) research priority by PIONEER, a European network of excellence for big data in PCa. Despite being a research priority, cancer survivorship lacks a clear and agreed definition, and there is a distinct paucity of patient-reported outcome (PRO) data available on the subject. Data collection on cancer survivorship depends on the availability and implementation of (validated) routinely collected patient-reported outcome measures... -
Cancer origin tracing and timing in two high-risk prostate cancers using multisample whole genome analysis: prospects for personalized medicine
CONCLUSIONS: PrCa evolutionary analysis allows tracking of anatomic site of origin, timing of cancer origin and spread, and distinction of metastatic-capable from non-metastatic subclones. This enables better identification of actionable targets for therapy. If extended to larger cohorts, it appears likely that similar analyses could add substantial biological insight and clinically relevant value. -
Identification of long noncoding RNAs with aberrant expression in prostate cancer metastases
Prostate cancer (PCa) is the second-most common cause of male cancer-related death in western industrialized countries, and the emergence of metastases is a key challenge in the treatment of PCa. Accumulating studies have shown that long noncoding RNAs (lncRNAs) play an important role in the regulation of diverse cellular and molecular processes during the development and progression of cancer. Here, we utilized a unique cohort of castration-resistant prostate cancer metastases (mCRPC) and... -
Unanswered questions in prostate cancer - findings of an international multi-stakeholder consensus by the PIONEER consortium
PIONEER is a European network of excellence for big data in prostate cancer consisting of 37 private and public stakeholders from 9 countries across Europe. Many progresses have been done in prostate cancer management, but unanswered questions in the field still exist, and big data could help to answer these questions. The PIONEER consortium conducted a two-round modified Delphi survey aiming at building consensus between two stakeholder groups - health-care professionals and patients with... -
Author Correction: The landscape of viral associations in human cancers
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Author Correction: Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
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Author Correction: Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
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Author Correction: Butler enables rapid cloud-based analysis of thousands of human genomes
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Author Correction: Comprehensive molecular characterization of mitochondrial genomes in human cancers
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Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
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Author Correction: Genomic basis for RNA alterations in cancer
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Author Correction: Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
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Author Correction: The evolutionary history of 2,658 cancers
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Author Correction: Pan-cancer analysis of whole genomes
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Author Correction: Patterns of somatic structural variation in human cancer genomes
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Author Correction: The repertoire of mutational signatures in human cancer
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How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis
CONCLUSION: Typically, PRS accuracy is comparable to PSA or family history with a pooled AUC value 0.63 indicating mediocre performance for PRS alone.
2022
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Author Correction: Inferring structural variant cancer cell fraction
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Author Correction: Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig
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Author Correction: Combined burden and functional impact tests for cancer driver discovery using DriverPower
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Author Correction: Genomic footprints of activated telomere maintenance mechanisms in cancer
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Author Correction: Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
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Author Correction: High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations
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Author Correction: Integrative pathway enrichment analysis of multivariate omics data
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Author Correction: A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns
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Author Correction: Pathway and network analysis of more than 2500 whole cancer genomes
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Author Correction: Divergent mutational processes distinguish hypoxic and normoxic tumours
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Retraction Note: CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus
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How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis
CONCLUSION: Typically, PRS accuracy is comparable to PSA or family history with a pooled AUC value 0.63 indicating mediocre performance for PRS alone. -
Nonmalignant AR-positive prostate epithelial cells and cancer cells respond differently to androgen
Prostate cancer research suffers from the lack of suitable models to study the role of normal cells in prostate carcinogenesis. To address this challenge, we developed a cell line model mimicking luminal prostate epithelial cells by modifying the immortalized prostate epithelial cell line RWPE-1 to constitutively express the androgen receptor (AR). RWPE-1-AR cells express known AR target genes, and exhibit coexpression of luminal and basal markers characteristic of transient amplifying cells,... -
The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates
CONCLUSIONS: Cells within regions of morphologically normal tissue (both BPH and non-BPH) can expand under selective pressure by mechanisms that are distinct from those occurring in adjacent cancer, but that are allied to the presence of cancer. Expansions, which are probably stromal in origin, are characterised by lack of recurrent driver mutations, by almost complete absence of structural variants/copy number alterations, and mutational processes similar to malignant tissue. Our findings have... -
miR-32 promotes MYC-driven prostate cancer
miR-32 is an androgen receptor (AR)-regulated microRNA, expression of which is increased in castration-resistant prostate cancer (PC). We have previously shown that overexpression of miR-32 in the prostate of transgenic mice potentiates proliferation in prostate epithelium. Here, we set out to determine whether increased expression of miR-32 influences growth or phenotype in prostate adenocarcinoma in vivo. We studied transgenic mice expressing MYC oncogene (hiMYC mice) to induce tumorigenesis... -
Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients
CONCLUSION: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery. -
Spatial analysis of histology in 3D: quantification and visualization of organ and tumor level tissue environment
Histological changes in tissue are of primary importance in pathological research and diagnosis. Automated histological analysis requires ability to computationally separate pathological alterations from normal tissue. Conventional histopathological assessments are performed from individual tissue sections, leading to the loss of three-dimensional context of the tissue. Yet, the tissue context and spatial determinants are critical in several pathologies, such as in understanding growth patterns...