A5010548573- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Glioma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Breast Cancer Treatment Studies
- Bioinformatics and Genomic Networks
- Mathematical Biology Tumor Growth
- RNA modifications and cancer
- Evolution and Genetic Dynamics
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Health and Medical Research Impacts
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- Cutaneous lymphoproliferative disorders research
- NF-κB Signaling Pathways
- T-cell and Retrovirus Studies
- Genomic variations and chromosomal abnormalities
- Radiopharmaceutical Chemistry and Applications
- Cell Image Analysis Techniques
- Microtubule and mitosis dynamics
Genomics (United Kingdom)
2015-2024
Institute of Cancer Research
2015-2024
Cancer Research UK
2007-2023
Institute of Cancer Research
2017
University of Cambridge
2008-2015
Evolutionary Genomics (United States)
2015
Imperial College London
2015
University of Bristol
2015
MultiMedica
2015
Cancer Research UK Cambridge Center
2009-2015
Glioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely key to understanding treatment failure. However, extent as result tumor evolution still poorly understood. To address this, we developed unique surgical multisampling scheme collect spatially distinct fragments from 11 GB patients. We present an integrated genomic analysis uncovers...
Cancer organoids to model therapy response are miniature, three-dimensional cell culture models that can be made from primary patient tumors and studied in the laboratory. Vlachogiannis et al. asked whether such “tumor-in-a-dish” approaches used predict drug responses clinic. They generated a live organoid biobank patients with metastatic gastrointestinal cancer who had previously been enrolled phase I or II clinical trials. This allowed authors compare how actually responded Encouragingly,...
Abstract Background MicroRNAs (miRNAs), a class of short non-coding RNAs found in many plants and animals, often act post-transcriptionally to inhibit gene expression. Results Here we report the analysis miRNA expression 93 primary human breast tumors, using bead-based flow cytometric profiling method. Of 309 miRNAs assayed, identify 133 expressed tumors. We used mRNA classify tumors as luminal A, B, basal-like, HER2+ normal-like. A number are differentially between these molecular tumor...
The mechanisms underlying microRNA (miRNA) disruption in human disease are poorly understood. In cancer cells, the transcriptional silencing of tumor suppressor genes by CpG island promoter hypermethylation has emerged as a common hallmark. We wondered if same epigenetic can "hit" miRNAs transformed cells. To address this issue, we have used cells genetically deficient for DNA methyltransferase enzymes combination with miRNA expression profiling. observed that hypomethylation induces release...
Chemical Entities of Biological Interest (ChEBI) is a freely available dictionary molecular entities focused on ‘small’ chemical compounds. The in question are either natural products or synthetic used to intervene the processes living organisms. Genome-encoded macromolecules (nucleic acids, proteins and peptides derived from by cleavage) not as rule included ChEBI. In addition entities, ChEBI contains groups (parts entities) classes entities. includes an ontological classification, whereby...
Sequential profiling of plasma cell-free DNA (cfDNA) holds immense promise for early detection patient progression. However, how to exploit the predictive power cfDNA as a liquid biopsy in clinic remains unclear. RAS pathway aberrations can be tracked monitor resistance anti-EGFR monoclonal antibodies patients with metastatic colorectal cancer. In this prospective phase II clinical trial single-agent cetuximab
Abstract Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity 1 . The interplay of these biological processes their respective contributions tumour evolution remain unknown. Here we show that genetic ancestry only infrequently affects gene expression traits subclonal in colorectal cancer (CRC). Using spatially resolved paired whole-genome transcriptome sequencing, find the majority variation is not strongly heritable but rather...
Abstract Colorectal malignancies are a leading cause of cancer-related death 1 and have undergone extensive genomic study 2,3 . However, DNA mutations alone do not fully explain malignant transformation 4–7 Here we investigate the co-evolution genome epigenome colorectal tumours at single-clone resolution using spatial multi-omic profiling individual glands. We collected 1,370 samples from 30 primary cancers 8 concomitant adenomas generated 1,207 chromatin accessibility profiles, 527 whole...
The increasing trend for incorporation of biological sample collection within clinical trials requires procedures which are convenient and acceptable both patients clinicians. This study investigated the feasibility using saliva-extracted DNA in comparison to blood-derived DNA, across two genotyping platforms: Applied Biosystems Taqman™ Illumina Beadchip™ genome-wide arrays.Patients were recruited from Pharmacogenetics Breast Cancer Chemotherapy (PGSNPS) study. Paired blood saliva samples...
Abstract Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving to one drug may come at a cost of decreased fecundity or increased sensitivity another drug. These evolutionary trade-offs can be exploited using ‘evolutionary steering’ control tumour population and delay resistance. recapitulating dynamics experimentally remains challenging. Here, we present an approach for steering based on combination single-cell barcoding,...
Abstract The dominant mutational signature in colorectal cancer genomes is C > T deamination (COSMIC Signature 1) and, a small subgroup, mismatch repair signatures 6 and 44). Mutations common driver genes are often not consistent with those signatures. Here we perform whole-genome sequencing of normal colon crypts from patients, matched to previous multi-omic tumour dataset. We analyse that were distant vs adjacent the cancer. In contrast healthy individuals, patients have high incidence...
The differential expression pattern of microRNAs (miRNAs) during mammary gland development might provide insights into their role in regulating the homeostasis epithelium. Our aim was to analyse these regulatory functions by deriving a comprehensive tissue-specific combined miRNA and mRNA profile post-natal mouse development.We measured 318 individual murine miRNAs bead-based flow-cytometric profiling whole glands throughout 16-point developmental time course, including juvenile, puberty,...
The accurate and high resolution mapping of DNA copy number aberrations has become an important tool by which to gain insight into the mechanisms tumourigenesis. There are various commercially available platforms for such studies, but there remains no general consensus as optimal platform. have been several previous platform comparison they either described older technologies, used less-complex samples, or not addressed issue inherent biases in comparisons. Here we describe a systematic data...
Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to therapy, leading relapse. Using patient-derived xenografts (PDXs), we observed that mCRC cells surviving EGFR inhibition exhibited gene expression patterns similar those a quiescent subpopulation normal intestinal secretory precursors Paneth cell characteristics. Compared...
BackgroundGlioblastoma is the most common and aggressive adult brain malignancy against which conventional surgery chemoradiation provide limited benefit. Even when a good treatment response obtained, recurrence inevitably occurs either locally (∼80%) or distally (∼20%), driven by cancer clones that are often genomically distinct from those in primary tumour. Glioblastoma cells display characteristic infiltrative phenotype, invading surrounding tissue spreading across whole brain. Cancer...
Abstract Both normal tissue development and cancer growth are driven by a branching process of cell division mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in humans remains challenging. Here, we show multi-sample genomic data from single time point tissues contains information on single-cell divisions. We present new theoretical framework that, applied whole-genome sequencing healthy cancer, allows inferring the rate...
Substantial evidence supports the concept that cancers are organized in a cellular hierarchy with cancer stem cells (CSC) at apex. To date, primary for CSCs derives from transplantation assays, which have known limitations. In particular, they unable to report on fate of within original human tumor. Because difficulty measuring tumor characteristics patients, organization and other aspects dynamics not been quantified directly, although likely play fundamental role progression therapy...
Abstract Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis genomic characterization revealed that SEZ harbors malignant cells tumor-initiating capacity, analogous to isolated from tumor mass (T). We observed resistance supramaximal chemotherapy doses along...
Abstract Circulating tumour DNA (ctDNA) allows tracking of the evolution human cancers at high resolution, overcoming many limitations tissue biopsies. However, exploiting ctDNA to determine how a patient’s cancer is evolving in order aid clinical decisions remains difficult. This because mix fragmented alleles, and contribution different deposits largely unknown. Profiling almost invariably requires prior knowledge what genomic alterations track. Here, we leverage on rapid autopsy programme...
Objective— We investigated the association between functional, epigenetic, and expressional profile of human adventitial progenitor cells (APCs) therapeutic activity in a model limb ischemia. Approach Results— Antigenic functional features were analyzed throughout passaging 15 saphenous vein (SV)–derived APC lines, which 10 from SV leftovers coronary artery bypass graft surgery 5 varicose removal. Moreover, SV-APC lines transplanted (8×10 cells, IM) mice with Blood flow capillary arteriole...