Marek Cmero
A5023110316- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- Genomics and Phylogenetic Studies
- Genetic factors in colorectal cancer
- Evolution and Genetic Dynamics
- Genomics and Rare Diseases
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Prostate Cancer Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Nutrition, Genetics, and Disease
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Genetics, Bioinformatics, and Biomedical Research
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- RNA Interference and Gene Delivery
The University of Melbourne
2015-2025
Walter and Eliza Hall Institute of Medical Research
2014-2023
Murdoch Children's Research Institute
2018-2022
The Royal Melbourne Hospital
2015-2022
Peter MacCallum Cancer Centre
2014-2021
Royal Children's Hospital
2020
Epworth Hospital
2020
Cancer Research UK
2018
Data61
2014-2016
St Vincents Institute of Medical Research
2014-2015
Cancer develops through a process of somatic evolution
Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, drivers ITH across cancer types are poorly understood. To address this, we extensively characterize whole-genome sequences 2,658 samples spanning 38 types. Nearly all informative (95.1%) contain evidence distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection driver mutations most...
Abstract Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality poorly understood. Here we reveal precise direction metastatic spread across four lethal patients using whole-genome ultra-deep targeted sequencing longitudinally collected tumours. We find one case surgical bed causing local recurrence, another cross-metastatic site seeding combining with dynamic...
Abstract Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as grade. To interrogate the evolutionary origins cancer heterogeneity, we analyzed 666 whole genomes. We identified a compendium 223 recurrently mutated driver regions, influencing downstream processes gene expression. validated individual germline variants that predispose tumors to acquire specific...
The objective of this study was to determine whether microRNA (miRNA) profiling urine could identify the presence urothelial carcinoma bladder (UCB) and compare its performance characteristics that cystoscopy.In discovery cohort we screened 81 patients, which included 21 benign controls, 30 non-recurrers patients with active cancer (recurrers), using a panel 12 miRNAs. Data analysis performed machine learning approach Support Vector Machine classifier Student's t-test feature selection...
The latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state which cells persist prior overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling retention cell dormancy. We demonstrate that loss type I IFN occurs proliferating bone. This suppresses tumor immunogenicity therapeutic response promotes activation drive progression....
Methods for detecting somatic genome rearrangements in tumours using next-generation sequencing are vital cancer genomics. Available algorithms use one or more sources of evidence, such as read depth, paired-end reads split to predict structural variants. However, the problem remains challenging due significant computational burden and high false-positive false-negative rates.In this article, we present Socrates (SOft Clip re-alignment To idEntify Structural variants), a highly efficient...
Summary Cancer develops through a process of somatic evolution. Here, we use whole-genome sequencing 2,778 tumour samples from 2,658 donors to reconstruct the life history, evolution mutational processes, and driver mutation sequences 39 cancer types. The early phases oncogenesis are driven by point mutations in small set genes, often including biallelic inactivation suppressors. Early is also characterised specific copy number gains, such as trisomy 7 glioblastoma or isochromosome 17q...
Abstract We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines allele frequencies both SV breakends, then simultaneously estimates and copy number. assess performance using in silico mixtures real samples, at known proportions, created two clonal metastases same patient. find that SVclone’s is comparable to single-nucleotide variant-based methods, despite having...
Abstract The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types co-occur in the same tumours. However, it remains unclear how processes change during evolution due to lack reliable methods reconstruct evolutionary trajectories mutational signature activity. Here, as part ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data from 2658...
SUMMARY Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin drivers ITH across cancer types are poorly understood. To address this question, we extensively characterize whole-genome sequences 2,658 samples, spanning 38 types. Nearly all informative samples (95.1%) contain evidence distinct subclonal expansions, with frequent branching relationships between subclones. We observe positive selection...
Calling fusion genes from RNA-seq data is well established, but other transcriptional variants are difficult to detect using existing approaches. To identify all types of in transcriptomes we developed MINTIE, an integrated pipeline for data. We take a reference-free approach, combining de novo assembly transcripts with differential expression analysis up-regulated novel case sample. compare MINTIE eight approaches, detecting > 85% while no method able achieve this. posit that will be new...
The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with restricted to nodes have a better prognosis than those metastatic spread, suggesting the possibility distinct aetiologies. To explore this, we traced patterns using tumour phylogenies inferred from genome-wide copy-number profiling 48 samples across 3 patients disease osseous disease. Our results show that cells regional originate evolutionary advanced extraprostatic rather...
<ns4:p><ns4:bold>Background:</ns4:bold> RNA sequencing has enabled high-throughput and fine-grained quantitative analyses of the transcriptome. While differential gene expression is most widely used application this technology, RNA-seq data also resolution to infer transcript usage (DTU), which can elucidate role different isoforms between experimental conditions, cell types or tissues. DTU typically been inferred from exon-count data, issues with assigning reads unambiguously counting bins,...
Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease over 70 years. Tumors eventually progress despite castration through a number well-characterized mechanisms; however, little known about what determines magnitude response to short-term inhibition.We evaluated novel combination AR-targeting (degarelix, abiraterone, bicalutamide) noted objective patient therapy was highly...
Abstract Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumor evolution, allowing an assessment how cancers initiate, progress and respond selective pressures. We launched the ICGC–TCGA (International Cancer Genome Consortium–The Atlas) DREAM Somatic Mutation Calling Tumor Heterogeneity Evolution Challenge benchmark existing subclonal algorithms. This 7-year community effort used cloud computing 31 on 51 simulated tumors. Algorithms were scored...
Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin drivers ITH across cancer types are poorly understood. To address this question, we extensively characterize whole-genome sequences 2,658 samples, spanning 38 types. Nearly all informative samples (95.1%) contain evidence distinct subclonal expansions, with frequent branching relationships between subclones. We observe positive selection driver...
Dendritic cells (DCs) are sentinel of the immune system and essential for inducing a proper response. The mechanisms driving development DCs not fully understood. Although roles cytokines transcription factors have been major focus, there is now substantial interest in role microRNAs (miRNAs). miRNAs small RNAs that regulate gene expression by targeting messenger translational repression ultimately degradation. By means deep sequencing, we assembled comprehensive quantitative resource miRNA...
Abstract We have characterised intra-tumour heterogeneity (ITH) across 2,778 whole genome sequences of tumours in the International Cancer Genome Consortium Pan-Cancer Analysis Whole Genomes project, representing 36 distinct cancer types. applied 6 copy number (CNA) callers and 11 subclonal reconstruction algorithms developed approaches to integrate results robust, high-confidence CNA calls architectures. The analysis reveals widespread ITH. find at least one subclone nearly all (96.7%) with...
We present SVclone, a computational method for inferring the cancer cell fraction of structural variant breakpoints from whole-genome sequencing data. validate our approach using simulated and real tumour samples, demonstrate its utility on 2,778 sequenced tumours. find subset liver, breast ovarian cases with decreased overall survival that have subclonally enriched copy-number neutral rearrangements, an observation could not be discovered currently available methods.
Background: RNA sequencing has enabled high-throughput and fine-grained quantitative analyses of the transcriptome. While differential gene expression is most widely used application this technology, RNA-seq data also resolution to infer transcript usage (DTU), which can elucidate role different isoforms between experimental conditions, cell types or tissues. DTU typically been inferred from exon-count data, issues with assigning reads unambiguously counting bins, requires alignment genome....