A5039180118- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Cervical Cancer and HPV Research
- Immunodeficiency and Autoimmune Disorders
- Cancer Genomics and Diagnostics
- Multiple Myeloma Research and Treatments
- Glycosylation and Glycoproteins Research
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Genital Health and Disease
- T-cell and Retrovirus Studies
- Reproductive tract infections research
- Advanced Breast Cancer Therapies
- Viral-associated cancers and disorders
- Cancer-related Molecular Pathways
- Genetic factors in colorectal cancer
- Genomic variations and chromosomal abnormalities
- Mast cells and histamine
- Urological Disorders and Treatments
- Urologic and reproductive health conditions
- Metabolism, Diabetes, and Cancer
- Genetic Syndromes and Imprinting
- Esophageal Cancer Research and Treatment
- IL-33, ST2, and ILC Pathways
University of Southampton
2016-2025
Southampton General Hospital
2019-2024
Cancer Research UK
2019-2022
University Hospital Southampton NHS Foundation Trust
2022
Cardiff University
2011-2015
Murray State University
1980
Abstract Despite advances in chronic lymphocytic leukaemia (CLL) treatment, globally chemotherapy remains a central treatment modality, with trials representing an invaluable resource to explore disease-related/genetic features contributing long-term outcomes. In 499 LRF CLL4 cases, trial >12 years follow-up, we employed targeted resequencing of 22 genes, identifying 623 mutations. After background mutation rate correction, 11/22 genes were recurrently mutated at frequencies between 3.6%...
The acquisition of N-glycosylation sites occupied by oligomannose-type glycans in the immunoglobulin complementarity-determining region (CDR) is an early clonal tumor-specific identifier follicular lymphoma (FL). CDR-located are also acquired germinal-center-B-cell-like diffuse large B-cell lymphomas (GCB-DLBCL), but their significance less defined. We used RNA-seq assembly to determine frequency and CDR location (AGS) two independent DLBCL cohorts. Composition occupying AGS was determined...
Abstract Chronic lymphocytic leukemia patients with mutated immunoglobulin heavy-chain genes (IGHV-M), particularly those lacking poor-risk genomic lesions, often respond well to chemoimmunotherapy (CIT). DNA methylation profiling can subdivide early-stage into naive B-cell–like CLL (n-CLL), memory (m-CLL), and intermediate (i-CLL), differing times first treatment overall survival. However, whether identify destined favorably CIT has not been ascertained. We classified treatment-naive (n =...
In understanding clonal evolution in cancer, whole genome sequencing (WGS) provides unparalleled data that can be leveraged to derive tumor phylogenies.Specifically, estimates of the cancer cell fraction (CCF), is cells bearing a set somatic mutations, highly informative by defining which mutations are and associated with most recent common ancestor (MRCA) all cells, occur subclonally as later events.By clustering observed based on their CCF subsequent phylogenetic tree inference, derived...
In classic Hairy cell leukaemia (HCLc), a single case has thus far been interrogated by whole exome sequencing (WES) in treatment naive patient, which BRAF V(600)E was identified as an acquired somatic mutation and confirmed occurring near-universally this form of disease conventional PCR-based cohort screens. It left open however the question whether other genome-wide mutations may also commonly occur at high frequency presentation HCLc disease. To address this, we have carried out WES 5...
// Graeme Cowan 1, * , Nicola J. Weston-Bell 2, Dean Bryant 2 Anja Seckinger 3 Dirk Hose Niklas Zojer 4 Surinder S. Sahota 1 Institute of Immunology and Infection Research, Centre for Immunity, Evolution, University Edinburgh, UK Tumour Immunogenetics Group, Cancer Sciences Academic Unit, Faculty Medicine, Southampton, Medizinische Klinik V, Universitätsklinikum Heidelberg, Germany Center Oncology Hematology, 1st Department Wilhelminenspital, Vienna, Austria These authors have contributed...
Abstract Purpose: Response rates to treatment of vulval intraepithelial neoplasia (VIN) with imiquimod and cidofovir are approximately 57% 61%, respectively. Treatment is associated significant side effects and, if ineffective, risk malignant progression. response not predicted by clinical factors. Identification a biomarker that could predict an attractive prospect. This work investigated HPV DNA methylation as potential predictive in this setting. Experimental Design: from 167 cases VIN 3...
Abstract The epiCMIT (epigenetically-determined Cumulative MIToses) mitotic clock traces B-cell history via DNA methylation changes in heterochromatin and H3K27me3-containing chromatin. While high scores correlated with poor outcomes CLL MCL, its prognostic significance SMZL remains unknown. Derived from 142 cases using microarrays, values were genomic, transcriptomic, clinical data. EpiCMIT as a continuous variable was significantly higher females ( p =0.02), patients IGHV1-2*04 allele...
Abstract Vulval intraepithelial neoplasia is a precursor of vulval carcinoma, and frequently associated with human papillomavirus (HPV) infection. Estimates HPV prevalence in vary widely the UK. The objective this study was to assess infection sample women neoplasia, confirmed histologically, determine proportion disease types targeted by prophylactic vaccines. assessed biopsies from 59 patients using Greiner Bio‐One PapilloCheck® DNA chip assay. Valid results were obtained for 54 cases....
Vulval intraepithelial neoplasia is a precursor of vulval cancer and commonly caused by infection with Human Papillomavirus (HPV). Development topical treatments for requires appropriate in vitro models. This study evaluated the feasibility primary culture biopsy tissue to produce cell lines use as A potentially immortal line was produced which gave rise three monoclonal lines. These were characterized HPV genomic integration viral gene expression using ligation-mediated PCR quantitative...
Abstract Chronic lymphocytic leukaemia (CLL) cells can express unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain (IGHV) genes with differing clinical behaviours, variable B cell receptor (BCR) signalling capacity and distinct transcriptional profiles. As it remains unclear how these differences reflect the tumour cells’ innate pre/post germinal centre origin their BCR competence, we applied mRNA/miRNA sequencing to 38 CLL cases categorised into three subsets by IGHV mutational...
Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) a major cause of exacerbations and can infect replicate within MCs. The primary site HRV infection the airway epithelium MCs localise to this increasing severity. susceptibility gene, IL-33, encodes an epithelial-derived cytokine released following its impact on MC responses has yet be determined. In study we investigated global response LAD2 IL-33...
Sarcocystosis was diagnosed in 41 eighteen-month-old heifers and steers. Clinical signs included anorexia, severe weight loss, nervousness, hypersalivation, lameness, hair loss on the extremities. Hair noticed especially at end of tail, where there complete switch, giving animals a "rat-tail" appearance. Consistent gross changes observed necropsy four affected generalized lymphadenopathy, erosions ulcerations oral cavity esophagus, laminitis. Microscopically, young cysts Sarcocystis sp were...
Abstract In follicular lymphoma (FL), surface immunoglobulin (sIg) carries mandatory N-glycosylation sites in the variable regions, inserted during somatic hypermutation. These glycosylation are tumor-specific, indicating a critical function FL. Added glycan unexpectedly terminates at high mannose (Mann) and confers capability for sIg-mediated interaction with local macrophage-expressed DC-SIGN lectin resulting low-level activation of upstream B-cell receptor signaling responses. Here we...
Aim: T-helper cells could play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), a common B-cell neoplasm. Although CLL can present soluble antigens targeted from receptor to via major histocompatibility complex (MHC) class II, recognized by some may be encountered particulate form. Here ability internalize and anti-immunoglobulin M (IgM) beads as model for interaction with was investigated. Methods: The effect anti-IgM on antigen presentation pathways analyzed...
Abstract Immunoglobulin (IG) gene analysis provides fundamental insight into B-cell receptor structure and function. In tumors, it can inform the cell of origin clinical outcomes. Its value has been established in two types chronic lymphocytic leukemia with unmutated or mutated IGHV genes is emerging other tumors. The traditional PCR-based techniques, which are labor-intensive, rely on attainment either a dominant sequence small number subclonal sequences do not allow automated matching...