A5024485705- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
- Bioinformatics and Genomic Networks
- Molecular Biology Techniques and Applications
- Circular RNAs in diseases
- Lung Cancer Treatments and Mutations
- RNA Research and Splicing
- Genetic factors in colorectal cancer
- MicroRNA in disease regulation
- Protein Degradation and Inhibitors
- Sarcoma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Hedgehog Signaling Pathway Studies
- Pituitary Gland Disorders and Treatments
- Extracellular vesicles in disease
- Chromatin Remodeling and Cancer
- Neurofibromatosis and Schwannoma Cases
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Cancer-related molecular mechanisms research
Research Triangle Park Foundation
2021
CRUK Lung Cancer Centre of Excellence
2015-2020
University College London
2013-2020
University of Cambridge
2013-2018
Granta Design (United Kingdom)
2018
Cancer Research UK Cambridge Center
2014-2018
Cancer Research UK
2012-2017
London Cancer
2015-2017
Queen Mary University of London
2008-2015
Addenbrooke's Hospital
2012-2013
The management of metastatic breast cancer requires monitoring the tumor burden to determine response treatment, and improved biomarkers are needed. Biomarkers such as antigen 15-3 (CA 15-3) circulating cells have been widely studied. However, cell-free DNA carrying tumor-specific alterations (circulating DNA) has not extensively investigated or compared with other in cancer.
Sizable genomic regions were screened and low-frequency mutations identified in circulating DNA of cancer patients using tagged-amplicon deep sequencing (TAm-Seq).
The tumor suppressor p53 is frequently mutated in human cancer. Common mutant (mutp53) isoforms can actively promote cancer through gain-of-function (GOF) mechanisms. We report that mutp53 prolongs TNF-α-induced NF-κB activation cultured cells and intestinal organoid cultures. Remarkably, when exposed to dextran sulfate sodium, mice harboring a germline mutation develop severe chronic inflammation persistent tissue damage, are highly prone inflammation-associated colon This GOF manifested by...
TP53 mutants (mutp53) are involved in the pathogenesis of most human cancers. Specific mutp53 proteins gain oncogenic functions (GOFs) distinct from tumor suppressor activity wild-type protein. Tumor-associated macrophages (TAMs), a hallmark solid tumors, typically correlated with poor prognosis. Here, we report non-cell-autonomous mechanism, whereby cancer cells reprogram to supportive and anti-inflammatory state. The colon harboring GOF selectively shed miR-1246-enriched exosomes. Uptake...
We report genetic aberrations that activate the ERK/MAP kinase pathway in 100% of posterior fossa pilocytic astrocytomas, with a high frequency gene fusions between KIAA1549 and BRAF among these tumours. These were identified from analysis focal copy number gains at 7q34, detected using Affymetrix 250K 6.0 SNP arrays. PCR sequencing confirmed presence five KIAA1549-BRAF fusion variants, along single SRGAP3 RAF1. The resulting genes lack auto-inhibitory domains RAF1, which are replaced...
Type 2 immunity plays an important role in host defense against helminths and toxins while driving allergic diseases. Despite progress understanding the biology of type immunity, fundamental mechanisms regulating immune module remain unclear. In contrast with structural recognition used by pattern receptors, immunogens are sensed through their functional properties. Functional theory has arisen as paradigm for initiation immunity. However, vast array structurally unrelated makes it...
Introduction Detection and monitoring of circulating tumor DNA (ctDNA) is rapidly becoming a diagnostic, prognostic predictive tool in cancer patient care. A growing number gene targets have been identified as diagnostic or actionable, requiring the development reliable technology that provides analysis multiple genes parallel. We developed InVision™ liquid biopsy platform which utilizes enhanced TAm-Seq™ (eTAm-Seq™) technology, an amplicon-based next generation sequencing method for...
Malignant astrocytomas (MA) are aggressive central nervous system tumors with poor prognosis. Activating mutation of BRAF (BRAF(V600E)) has been reported in a subset these tumors, especially children. We have investigated the incidence BRAF(V600E) additional pediatric patient cohorts and examined effects blockade preclinical models wild-type MA.BRAF(V600E) status was two MA cohorts. For functional studies, cell lines were used to investigate shRNA knockdown vitro, pharmacologic inhibition...
VHL is mutated in the majority of patients with clear cell renal carcinoma (ccRCC), conflicting clinical relevance. Recent studies have identified recurrent mutations histone modifying and chromatin remodeling genes, including BAP1, PBRM1, SETD2, KDM6A , JARID1c . Current evidence suggests that BAP1 are associated aggressive disease. The significance remaining genes unknown. In this study, targeted sequencing (entire genes) coding regions SETD2 was performed on 132 ccRCCs matched normal...
Abstract Muscle Invasive Bladder Cancer (MIBC) has a poor prognosis. Whilst patients can achieve 6% improvement in overall survival with Neo-Adjuvant Chemotherapy (NAC), many do not respond. Body fluid mutant DNA (mutDNA) may allow non-invasive identification of treatment failure. We collected 248 liquid biopsy samples including plasma, cell pellet (UCP) and supernatant (USN) from spun urine, 17 undergoing NAC. assessed single nucleotide variants copy number alterations mutDNA using...
Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses targeted therapies have been observed with actionable mutations detected plasma at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation required. We developed the InVisionFirst™ assay, an based on...
Head and neck squamous cell carcinoma (HNSCC) remain a substantial burden to global health. Cell-free circulating tumour DNA (ctDNA) is an emerging biomarker but has not been studied sufficiently in HNSCC.We conducted single-centre prospective cohort study investigate ctDNA patients with p16-negative HNSCC who received curative-intent primary surgical treatment. Whole-exome sequencing was performed on formalin-fixed paraffin-embedded (FFPE) tissue. We utilised RaDaRTM, highly sensitive...
Despite the importance of RAS-RAF-MAPK pathway in normal physiology and disease numerous organs, its role during pituitary development tumourigenesis remains largely unknown. Here we show that over-activation MAPK pathway, through conditional expression gain-of-function alleles BrafV600E KrasG12D developing mouse pituitary, results severe hyperplasia abnormal morphogenesis gland by end gestation. Cell-lineage commitment terminal differentiation are disrupted, leading to a significant...
Glioneuronal tumours are an important cause of treatment-resistant epilepsy. Subtypes tumour often poorly discriminated by histological features and may be difficult to diagnose due a lack robust diagnostic tools. This is illustrated marked variability in the reported frequencies across different epilepsy surgical series. To address this, we used DNA methylation arrays RNA sequencing assay expression profiles within large cohort glioneuronal tumours. By adopting class discovery approach,...
Research Article30 May 2018Open Access Transparent process Dynamics of multiple resistance mechanisms in plasma DNA during EGFR-targeted therapies non-small cell lung cancer Dana Wai Yi Tsui orcid.org/0000-0002-0595-6664 Cancer UK Cambridge Institute, Li Ka Shing Centre, University Cambridge, Major Center - Search for more papers by this author Muhammed Murtaza Department Oncology, Alvin Seng Cheong Wong Haematology-Oncology, National Health System, Singapore, Singapore Oscar M Rueda...
Gene fusions involving members of the RAF family protein kinases have recently been identified as characteristic aberrations low-grade astrocytomas, most common tumors central nervous system in children. While it has shown that these cause constitutive activation ERK/MAPK pathway, very little is known about their formation. Here, we present a detailed analysis gene fusion breakpoints from well-characterized cohort 43 astrocytomas. Our findings show rearrangements generate may be simple or...
This study tested the claim that digital PCR (dPCR) can offer highly reproducible quantitative measurements in disparate laboratories. Twenty-one laboratories measured four blinded samples containing different quantities of a KRAS fragment encoding G12D, an important genetic marker for guiding therapy certain cancers. is challenging to quantify reproducibly using (qPCR) or next generation sequencing (NGS) due presence competing wild type sequences and need calibration. Using dPCR, 18 were...