Ben Kinnersley
A5082417116- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Ferroptosis and cancer prognosis
- Bioinformatics and Genomic Networks
- MicroRNA in disease regulation
- DNA Repair Mechanisms
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- BRCA gene mutations in cancer
- Radiomics and Machine Learning in Medical Imaging
- RNA Research and Splicing
- Genomics and Rare Diseases
- Acute Lymphoblastic Leukemia research
- Molecular Biology Techniques and Applications
- Multiple Myeloma Research and Treatments
- Genomic variations and chromosomal abnormalities
- Cancer Immunotherapy and Biomarkers
- Renal cell carcinoma treatment
- Chronic Lymphocytic Leukemia Research
- Gene expression and cancer classification
Institute of Cancer Research
2016-2025
University College London
2022-2025
CRUK Lung Cancer Centre of Excellence
2022-2025
Cancer Institute (WIA)
2023-2024
Institute of Cancer Research
2017-2023
London Cancer
2022-2023
University College Hospital
2023
Royal Marsden NHS Foundation Trust
2020-2022
Amgen (United States)
2019
MRC Epidemiology Unit
2017
Abstract Colorectal carcinoma (CRC) is a common cause of mortality 1 , but comprehensive description its genomic landscape lacking 2–9 . Here we perform whole-genome sequencing 2,023 CRC samples from participants in the UK 100,000 Genomes Project, thereby providing highly detailed somatic mutational this cancer. Integrated analyses identify more than 250 putative driver genes, many not previously implicated or other cancers, including several recurrent changes outside coding genome. We...
Abstract Colorectal cancer (CRC) displays a complex pattern of inheritance. It is postulated that much the missing heritability CRC enshrined in high-impact rare alleles, which are mechanistically and clinically important. In this study, we assay impact germline mutations on CRC, analysing high-coverage exome sequencing data 1,006 early-onset familial cases 1,609 healthy controls, with additional array up to 5,552 6,792 controls. We identify highly penetrant 16% CRC. Although majority these...
Abstract Genome-wide association studies (GWAS) have led to the identification of hundreds susceptibility loci across cancers, but impact further remains uncertain. Here we analyse summary-level data from GWAS European ancestry fourteen cancer sites estimate number common variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree polygenicity, involving at minimum thousands loci. We project that sample sizes required explain 80% heritability vary 60,000...
The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but preferentially protected transcription-coupled repair
Abstract The value of genome-wide over targeted driver analyses for predicting clinical outcomes cancer patients is debated. Here, we report the whole-genome sequencing 485 chronic lymphocytic leukemia enrolled in trials as part United Kingdom’s 100,000 Genomes Project. We identify an extended catalog recurrent coding and noncoding genetic mutations that represents a source future studies provide most complete high-resolution map structural variants, copy number changes global genome...
Tumor genomic profiling is increasingly seen as a prerequisite to guide the treatment of patients with cancer. To explore value whole-genome sequencing (WGS) in broadening scope cancers potentially amenable precision therapy, we analysed data on 10,478 spanning 35 cancer types recruited UK 100,000 Genomes Project. We identified 330 candidate driver genes, including 74 that are new any estimate approximately 55% studied harbor at least one clinically relevant mutation, predicting either...
Knowledge of the contribution high-penetrance susceptibility to familial colorectal cancer (CRC) is relevant counseling, treatment, and surveillance CRC patients families.
Abstract Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much the heritable risk remains unidentified. Here, we perform a GWAS and conduct meta-analysis with two existing GWAS, totaling 2442 cases 14,609 controls. We identify loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10 −9 , odds ratio (OR) 1.34) ETV6-RUNX1 fusion-positive 2q22.3 (rs17481869, 3.20 −8 OR 2.14). Our findings...
Abstract Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones women as potential protective factors for these tumors, with inconsistent results. genome-wide association studies (GWAS) not stratified by sex. Potential sex-specific genetic effects were assessed autosomal SNPs and chromosome variants all glioma, GBM non-GBM patients using data from four previous GWAS. Datasets analyzed sex-stratified logistic regression...
We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. identified five individuals with MBD4 within four families and these had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, uveal melanoma. encodes glycosylase involved G:T mismatches resulting from deamination 5'-methylcytosine. The adenomas MBD4-deficient showed mutator...
Recent genome-wide association studies of glioma have led to the discovery single nucleotide polymorphisms (SNPs) at 25 loci influencing risk. Gliomas are heterogeneous, hence investigate relationship between risk SNPs and subtype we analysed 1659 tumours profiled for IDH mutation, TERT promoter mutation 1p/19q co-deletion. These data allowed definition five molecular subgroups glioma: triple-positive (IDH mutated, co-deletion, mutated); TERT-IDH 1p/19q-wild-type); IDH-only wild-type,...
An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated atopy to assess the using Mendelian randomisation (MR), approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. Two-sample MR was undertaken genome-wide association study data. used single nucleotide polymorphisms (SNPs) atopic...
Abstract Background Telomere maintenance is increasingly recognized as being fundamental to glioma oncogenesis with longer leukocyte telomere length (LTL) reported increase risk of glioma. To gain further insight into the relationship between genetics and glioma, we conducted several complementary analyses, using genome-wide association studies data on LTL (78 592 individuals) (12 488 cases 18 169 controls). Methods We performed both classical summary Mendelian randomization (SMR), coupled...
ABSTRACT Whole genome sequencing (WGS) allows exploration of the complete compendium oncogenic processes generating characteristic patterns mutations. Mutational signatures provide clues to tumour aetiology and highlight potentially targetable pathway defects. Here, alongside single base substitution (SBS), double (DBS), small insertions deletions (ID) copy number aberration (CN) covered by Catalogue Somatic Mutations in Cancer (COSMIC) we report from an additional mutation type, structural...
We have previously identified tagSNPs at 8q24.21 influencing glioma risk. sought to fine-map the location of functional basis this association using data from four genome-wide studies, comprising a total 4147 cases and 7435 controls. To improve marker density across 700 kb region, we imputed genotypes 1000 Genomes Project high-coverage sequencing generated on 253 individuals. Analysis revealed an low-frequency SNP rs55705857 (P = 2.24 × 10−38) which was sufficient fully capture association....