A5074940815- Sarcoma Diagnosis and Treatment
- Bone Tumor Diagnosis and Treatments
- Oral and Maxillofacial Pathology
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Soft tissue tumor case studies
- Chromatin Remodeling and Cancer
- Musculoskeletal synovial abnormalities and treatments
- Cardiac tumors and thrombi
- Tumors and Oncological Cases
- Molecular Biology Techniques and Applications
- Neurofibromatosis and Schwannoma Cases
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Vascular Tumors and Angiosarcomas
- Neuroblastoma Research and Treatments
- MicroRNA in disease regulation
- Lymphoma Diagnosis and Treatment
- Bioinformatics and Genomic Networks
- Histiocytic Disorders and Treatments
- Orthopedic Infections and Treatments
- Genomics and Rare Diseases
- Gene expression and cancer classification
- Urologic and reproductive health conditions
Royal National Orthopaedic Hospital
2016-2025
University College London
2016-2025
London Cancer
2023-2025
Royal National Orthopaedic Hospital NHS Trust
2013-2024
European Bioinformatics Institute
2024
Genomics England
2024
Boston Children's Hospital
2024
Stanmore College
2010-2023
Cancer Institute (WIA)
2023
National Cancer Institute
2015
Somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur gliomas acute myeloid leukaemia (AML). Since patients with multiple enchondromas have occasionally been reported to these conditions, we hypothesized that the same would cartilaginous neoplasms. Approximately 1200 mesenchymal tumours, including 220 222 osteosarcomas another ∼750 bone soft tissue were screened for IDH1 R132 mutations, using Sequenom(®) mass spectrometry. Cartilaginous tumours chondroblastic osteosarcomas,...
The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that caused somatic mosaicism for a mutation lethal in nonmosaic state.
PURPOSE: Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue malignancy of children and adolescents. Most ARMS patients express PAX3-FKHR or PAX7-FKHR gene fusions resulting from t(2;13) t(1;13) translocations, respectively. We wished to confirm the diagnostic specificity fusion detection in a large cohort RMS evaluate whether these alterations influence clinical outcome ARMS. PATIENTS AND METHODS: determined status 171 childhood (RMS) entered onto Intergroup Rhabdomyosarcoma Study...
Chordomas are malignant tumours that occur along the spine and thought to derive from notochordal remnants. There is significant morphological variability between within chordomas, with some showing prominent areas of chondroid differentiation. Our microarray data a broad range connective tissue neoplasms indicate that, at transcriptional level, chordomas resemble cartilaginous neoplasms. Here we show express many genes known be involved in cartilage development, but they also uniquely...
BackgroundFor many years, first-line treatment for locally advanced or metastatic soft-tissue sarcoma has been doxorubicin. This study compared gemcitabine and docetaxel versus doxorubicin as sarcoma.MethodsThe GeDDiS trial was a randomised controlled phase 3 done in 24 UK hospitals one Swiss Group Clinical Cancer Research (SAKK) hospital. Eligible patients had histologically confirmed of Trojani grade 2 3, disease progression before enrolment, no previous chemotherapy any cancer. Patients...
Abstract Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study osteosarcoma to date, comprising 112 childhood adult tumours encompassing all major histological subtypes. A key finding our identification mutations in insulin-like growth factor (IGF) signalling genes 8/112 (7%) cases. We validate this observation using fluorescence situ hybridization (FISH) an additional 87 osteosarcomas, with IGF1 receptor ( IGF1R )...
<h3>Importance</h3> Osteosarcoma, the most common malignant bone tumor in children and adolescents, occurs a high number of cancer predisposition syndromes that are defined by highly penetrant germline mutations. The genetic susceptibility to osteosarcoma outside familial remains unclear. <h3>Objective</h3> To investigate architecture 1244 patients with osteosarcoma. <h3>Design, Setting, Participants</h3> Whole-exome sequencing (n = 1104) or targeted 140) DNA from 10 participating...
Giant cell tumor of bone (GCTB) is a locally aggressive subarticular tumor. Having recently reported that H3.3 G34W mutations are characteristic this type, we have now investigated the sensitivity and specificity anti-histone rabbit monoclonal antibody in wide variety tumors including histologic mimics GCTB to assess its value as diagnostic marker. We also determined incidence G34 primary malignant assessed by genotype immunostaining. A total 3163 were tested. Totally, 213/235 (90.6%) showed...
Axial chordoma represents approximately 1% of malignant bone tumors. This tumor expresses cytokeratins, specifically cytokeratin 19, and commonly S100. More recently brachyury, a transcription factor important in mesodermal differentiation, including notochord development, has been detected by immunohistochemistry axial chordomas hemangioblastomas but not chondrosarcomas or other neoplasms. In this report, we describe 10 cases (6 men, 4 women: age 18 to 68 y; mean 44.6) extra-axial tumors, 8...
A variety of analyses, including fluorescence in situ hybridization (FISH), quantitative PCR (qPCR) and array CGH (aCGH), have been performed on a series chordomas from 181 patients. Twelve (7%) tumours displayed amplification the T locus an additional two cases showed focal amplification; 70/181 (39%) were polysomic for chromosome 6, 8/181 (4.5%) primary minor allelic gain as assessed by FISH. No germline alteration was identified non-neoplastic tissue 40 Copy number seen similar percentage...
Driver mutations in the two histone 3.3 (H3.3) genes, H3F3A and H3F3B, were recently identified by whole genome sequencing 95% of chondroblastoma (CB) targeted gene 92% giant cell tumour bone (GCT). Given high prevalence these driver mutations, it may be possible to utilise alterations as diagnostic adjuncts clinical practice. Here, we explored spectrum H3.3 a wide range large number tumours (n = 412) determine if could used distinguish GCT from other osteoclast-rich such aneurysmal cyst,...
Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases sporadic chordoma. We reveal duplications transcription factor brachyury (T) in up to 27% cases. These variants recapitulate rearrangement architecture pathogenic germline T that underlie familial In addition, find potentially clinically actionable PI3K signalling mutations 16% Intriguingly, one most frequently altered genes, mutated exclusively...
Aims We recently reported that 95% of chondroblastomas harbour a p.K36M mutation in either H3F3A (chromosome 1) or H3F3B 17), with the majority involving . The aim this study was to assess expression K36M‐mutated protein by immunohistochemistry large group tumours. Methods and results One thousand eight hundred ninety‐four tumours, including 85 10 clear‐cell chondrosarcomas, were studied; these, 82 one chondrosarcoma known H3F3 expressed mutated protein. Three nine chondrosarcomas wild type...
The transcription factor FOS has long been implicated in the pathogenesis of bone tumours, following discovery that viral homologue, v-fos, caused osteosarcoma laboratory mice. However, mutations have not found human bone-forming tumours. Here, we report recurrent rearrangement and its paralogue, FOSB, most common benign tumours bone, osteoblastoma osteoid osteoma. Combining whole-genome DNA RNA sequences, find five FOSB one tumour. Extending our findings into a cohort 55 cases, using FISH...
Neurofibromatosis 1 (NF1) leads to the development of benign and malignant peripheral nerve sheath tumors (MPNST). MPNST have been described develop in preexisting plexiform neurofibromas (PN) a poor prognosis. Atypical (ANF) were recently as precursor lesions for MPNST, making early detection management ANF possible strategy prevent MPNST. We aimed clinically characterize identify approaches. analyzed clinical, imaging, pathology findings all patients with NF1 at 3 institutions. Sixty-three...
Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one the highest burdens structural aberrations across human cancer. Here, we sought to unravel molecular basis complexity in by integrating DNA sequencing, ploidy analysis, gene expression, methylation profiling. We identified whole genome duplication as a prevalent pernicious force USARC tumorigenesis. Using mathematical...