Geoff Macintyre
A5048069780- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- Genomics and Phylogenetic Studies
- Ovarian cancer diagnosis and treatment
- Genetics, Bioinformatics, and Biomedical Research
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- Molecular Biology Techniques and Applications
- Evolution and Genetic Dynamics
- Gene expression and cancer classification
- Genomic variations and chromosomal abnormalities
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- Genomics and Rare Diseases
- Single-cell and spatial transcriptomics
- DNA Repair Mechanisms
- Prostate Cancer Diagnosis and Treatment
- Chromosomal and Genetic Variations
- Hormonal and reproductive studies
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Nutrition, Genetics, and Disease
Spanish National Cancer Research Centre
2020-2025
Centro de Investigación del Cáncer
2025
Cancer Research UK
2015-2024
University of Cambridge
2015-2024
Cancer Research UK Cambridge Center
2017-2023
Centro Nacional de Investigaciones Científicas
2021-2023
The University of Melbourne
2009-2020
Data61
2009-2018
Peter MacCallum Cancer Centre
2010-2014
Walter and Eliza Hall Institute of Medical Research
2014
Cancer develops through a process of somatic evolution
Abstract A key mutational process in cancer is structural variation, which rearrangements delete, amplify or reorder genomic segments that range size from kilobases to whole chromosomes 1–7 . Here we develop methods group, classify and describe somatic variants, using data the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium International Cancer Genome (ICGC) The Atlas (TCGA), aggregated whole-genome sequencing 2,658 cancers across 38 tumour types 8 Sixteen signatures variation...
Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies selected types have suggested chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium International Cancer Genome (ICGC) The Atlas (TCGA), we analyze patterns across 2,658 tumors 38 using whole-genome sequencing We find...
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 About half of all cancers have somatic integrations retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms retrotransposition 2,954 cancer genomes from 38 histological subtypes within framework Pan-Cancer Analysis Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired events, which affected 35% samples spanned a range event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as first...
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...
Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, boundaries separating different have important roles in reinforcing stability of these features. Indeed, domain disruptions human cancers can lead misregulation gene expression. However, frequency remains unclear. Here, as part Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium International...
Emerging evidence suggests that poor glycemic control mediates post-translational modifications to the H3 histone tail. We are only beginning understand dynamic role of some diverse epigenetic changes mediated by hyperglycemia at single loci, yet elevated glucose levels thought regulate genome-wide changes, and this still remains poorly understood. In article we describe H3K9/K14 hyperacetylation DNA methylation maps conferred in primary human vascular cells. Chromatin immunoprecipitation...
Abstract Motivation: Determining the functional impact of non-coding disease-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) is challenging. Many these SNPs are likely to be regulatory (rSNPs): variations which affect ability a transcription factor (TF) bind DNA. However, experimental procedures for identifying rSNPs expensive and labour intensive. Therefore, in silico methods required rSNP prediction. By scoring two alleles with TF...
The Illumina HumanMethylation450 BeadChip (HM450K) measures the DNA methylation of 485,512 CpGs in human genome. technology relies on hybridization genomic fragments to probes chip. However, certain factors may compromise ability measure using array such as single nucleotide polymorphisms (SNPs), small insertions and deletions (INDELs), repetitive DNA, regions with reduced complexity. Currently, there is no clear method or pipeline for determining which HM450K bead should be retained...
Abstract Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative lengthening associated with ATRX DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium , we dissect whole-genome sequencing data over 2500 matched tumor-control samples from 36 different tumor types aggregated within to characterize genomic footprints these mechanisms. While content tumors mutations...
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...
Abstract The drivers of recurrence and resistance in ovarian high grade serous carcinoma remain unclear. We investigate the acquisition by collecting tumour biopsies from a cohort 276 women with relapsed BriTROC-1 study. Panel sequencing shows close concordance between diagnosis relapse, only four discordant cases. There is also very strong copy number no significant difference purity, ploidy or focal somatic alterations, even when stratified platinum sensitivity prior chemotherapy lines....
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...
Abstract Purpose: Gene expression–based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation clinical utility has been hindered by nonstandardized methods, which are not applicable in a setting. We sought to generate grade minimal gene set assay classification individual tumor specimens into HGSOC and confirm previously reported subtype-associated...
Abstract While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 from 26 cases with platinum-resistant TGCT, combine this published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level focal (CN) events, SNV CN signatures. Albeit preliminary...
High-grade serous ovarian carcinoma (HGSOC) is the most genomically complex cancer, characterized by ubiquitous
Abstract Cancer cells often exhibit DNA copy number aberrations and can vary widely in their ploidy. Correct estimation of the ploidy single-cell genomes is paramount for downstream analysis. Based only on sequencing information, scAbsolute achieves accurate unbiased measurement replication status, including whole-genome duplications. We demonstrate scAbsolute’s capabilities using experimental cell multiplets, a FUCCI cycle expression system, benchmark against state-of-the-art methods....
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...