Adrienne M. Flanagan
A5049499439- Sarcoma Diagnosis and Treatment
- Bone Tumor Diagnosis and Treatments
- Cancer Genomics and Diagnostics
- Oral and Maxillofacial Pathology
- Bone health and treatments
- Cancer-related molecular mechanisms research
- Bone Metabolism and Diseases
- RNA modifications and cancer
- Neurofibromatosis and Schwannoma Cases
- Soft tissue tumor case studies
- Protein Degradation and Inhibitors
- Chromatin Remodeling and Cancer
- Genomic variations and chromosomal abnormalities
- Musculoskeletal synovial abnormalities and treatments
- Neuroblastoma Research and Treatments
- Advanced Breast Cancer Therapies
- Genomics and Chromatin Dynamics
- Osteoarthritis Treatment and Mechanisms
- Cancer, Hypoxia, and Metabolism
- Molecular Biology Techniques and Applications
- Vascular Tumors and Angiosarcomas
- Epigenetics and DNA Methylation
- Cardiac tumors and thrombi
- Genomics and Rare Diseases
- Knee injuries and reconstruction techniques
University College London
2016-2025
London Cancer
2016-2025
Royal National Orthopaedic Hospital
2016-2025
Royal National Orthopaedic Hospital NHS Trust
2015-2024
CRUK Lung Cancer Centre of Excellence
2015-2024
European Bioinformatics Institute
2024
Genomics England
2024
Boston Children's Hospital
2024
Stanmore College
2004-2023
MRC Laboratory for Molecular Cell Biology
2023
Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which term chromothripsis, whereby tens hundreds of genomic rearrangements occur in one-off cellular crisis. Rearrangements involving one or few chromosomes crisscross back forth across involved regions, generating frequent oscillations between two copy number states. These hallmarks...
The discovery of mutations in cancer genes has advanced our understanding cancer. These results are dispersed across the scientific literature and with availability human genome sequence will continue to accrue. COSMIC (Catalogue Somatic Mutations Cancer) database website have been developed store somatic mutation data a single location display other information related To populate this resource, currently extracted from reports for four genes, BRAF, HRAS, KRAS2 NRAS. At present, holds on 66...
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,...
Autologous chondrocyte implantation (ACI) is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations original periosteum-cover technique include use porcine-derived type I/type III collagen cover (ACI-C) matrix-induced autologous (MACI) using bilayer seeded with chondrocytes. We have performed prospective, randomised comparison ACI-C MACI knee in 91 patients, whom 44 received 47 grafts. Both treatments resulted improvement clinical score after...
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...
High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. The European American Osteosarcoma Study (EURAMOS)-1 collaboration of four study groups aiming to improve outcomes this rare disease by facilitating randomised controlled trials.Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high-grade in which case complete surgical resection at all sites was deemed be possible. A three-drug combination methotrexate, doxorubicin...
Abstract Protein kinases are frequently mutated in human cancer and inhibitors of mutant protein have proven to be effective anticancer drugs. We screened the coding sequences 518 (∼1.3 Mb DNA per sample) for somatic mutations 26 primary lung neoplasms seven cell lines. One hundred eighty-eight were detected 141 genes. Of these, 35 synonymous (silent) changes. This result indicates that most 188 “passenger” not causally implicated oncogenesis. However, an excess ∼40 nonsynonymous...
Recent sequencing studies have extensively explored the somatic alterations present in nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, origins impact cancer-associated mutations mtDNA are unclear. In this study, we analyzed from 1675 tumors. We identified 1907 substitutions, which exhibited dramatic replicative strand bias, predominantly C > T A G on mitochondrial heavy strand. This strand-asymmetric signature differs those found cancer but matches...
Introduction The human genome is peppered with mobile repetitive elements called long interspersed nuclear element–1 (L1) retrotransposons. Propagating through RNA and cDNA intermediates, these molecular parasites copy insert themselves throughout the genome, potentially disruptive effects on neighboring genes or regulatory sequences. In germ line, unique sequence downstream of L1 can also be retrotransposed if transcription continues beyond repeat, a process known as 3′ transduction. There...
Abstract Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents children. They represent a morphologically heterogeneous class of some entities lack defining histopathological features. Therefore, the diagnosis sarcomas is burdened with high inter-observer variability misclassification rate. Here, we demonstrate classification using machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma trained dataset 1077 profiles from...
Abstract Gains and losses of DNA are prevalent in cancer emerge as a consequence inter-related processes replication stress, mitotic errors, spindle multipolarity breakage–fusion–bridge cycles, among others, which may lead to chromosomal instability aneuploidy 1,2 . These copy number alterations contribute initiation, progression therapeutic resistance 3–5 Here we present conceptual framework examine the patterns human that is widely applicable diverse data types, including whole-genome...
Four international study groups undertook a large in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based histological response.Patients with osteosarcoma aged ≤40 years were treated MAP regimen, comprising pre-operatively 5-week cycles cisplatin 120 mg/m(2), doxorubicin 75 methotrexate 12 g/m(2) × 2 (MAP) and post-operatively further just MA. Patients after surgery. Those ≥10% viable...
Abstract Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following vivo exposure to ionizing have not been documented. Here, we searched for 12 radiation-associated second malignancies different tumour types. Two somatic mutation characterize irrespective type. Compared with 319 radiation-naive tumours, tumours carry median extra 201 deletions genome-wide, sized 1–100 base pairs often microhomology at the...
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 )...