A5084133067- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Chronic Lymphocytic Leukemia Research
- Glioma Diagnosis and Treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Melanoma and MAPK Pathways
- Cancer Treatment and Pharmacology
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Lung Cancer Treatments and Mutations
- Genomics and Phylogenetic Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Hepatocellular Carcinoma Treatment and Prognosis
- Genomic variations and chromosomal abnormalities
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Radiomics and Machine Learning in Medical Imaging
- Phytochemical compounds biological activities
- Malaria Research and Control
University of Arkansas for Medical Sciences
2016-2025
Institute of Cancer Research
2010-2023
Winthrop Rockefeller Foundation
2020-2023
Oxford University Press (United Kingdom)
2020
RIKEN Center for Integrative Medical Sciences
2015-2018
Wessex Regional Genetics Laboratory
2011
University of Leeds
2011
Newcastle University
2011
University of Southampton
2011
BAE Systems (Sweden)
2007
At the molecular level, myeloma is characterized by copy number abnormalities and recurrent translocations into immunoglobulin heavy chain locus. Novel methods, such as massively parallel sequencing, have begun to describe pattern of tumor-acquired mutations, but their clinical relevance has yet be established.We performed whole-exome sequencing for 463 patients who presented with were enrolled onto National Cancer Research Institute Myeloma XI trial, whom complete cytogenetic outcome data...
Patients with newly diagnosed multiple myeloma (NDMM) high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used identify patients, each which has significant weaknesses. Inclusion molecular into risk stratification could resolve current challenges. In a genome-wide analysis largest set and clinical data established date from NDMM, as part Myeloma Genome Project, we defined DNA drivers...
Abstract In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of “fitter” clones may be anticipated. However, an imbalanced distribution frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into spatial clonal architecture. We demonstrate genomic heterogeneity more than 75% patients,...
Highlights•Biliary tract cancers are clinically and genetically heterogeneous.•32 significantly mutated genes were identified, some negatively affecting prognosis.•A novel deletion of MUC17 at 7q22.1 was detected.•Cell-of-origin predictions suggest hepatocyte-origin hepatitis-related ICCs.•Deleterious germline mutations cancer-predisposing detected in 11% patients with BTC.Graphical abstractAbstractBackground & AimsBiliary (BTCs) pathologically heterogeneous respond poorly to treatment....
We have sequenced 463 presenting cases of myeloma entered into the UK Myeloma XI study using whole exome sequencing. Here we identify mutations induced as a consequence misdirected AID in partner oncogenes IGH translocations, which are activating and associated with impaired clinical outcome. An APOBEC mutational signature is seen 3.8% linked to translocation-mediated deregulation MAF MAFB, known poor prognostic factor. Patients this an increased load prognosis. Loss or MAFB expression...
Secondary MYC translocations in myeloma have been shown to be important the pathogenesis and progression of disease. Here, we used a DNA capture massively parallel sequencing approach identify partner chromosomes 104 presentation samples. 8q24 breakpoints were identified 21 (20%) samples with loci including IGH, IGK IGL, which juxtapose immunoglobulin (Ig) enhancers next 8/23 The remaining had XBP1, FAM46C, CCND1 KRAS, are B-cell maturation or pathogenesis. Analysis region surrounding...
Abstract Purpose: Regions on 1p with recurrent deletions in presenting myeloma patients were examined the purpose of defining and assessing their survival impact. Experimental Design: Gene mapping, gene expression, FISH, mutation analyses conducted patient samples from MRC Myeloma IX trial correlated clinical outcome data. Results: 1p32.3 was deleted 11% cases, deletion strongly associated impaired overall (OS) treated autologous stem cell transplant (ASCT). In less intensively,...
Epigenetic dysregulation is known to be an important contributor myeloma pathogenesis but, unlike other B-cell malignancies, the full spectrum of somatic mutations in epigenetic modifiers has not been reported previously. We sought address this using results from whole-exome sequencing context a large prospective clinical trial newly diagnosed patients and targeted cohort previously treated for comparison.
Smoldering myeloma (SMM) is associated with a high-risk of progression to (MM). We report the results study 82 patients both targeted sequencing that included capture immunoglobulin and MYC regions. By comparing these newly diagnosed (MM) we show fewer NRAS FAM46C mutations together adverse translocations, del(1p), del(14q), del(16q), del(17p) in SMM consistent their role as drivers transition MM. KRAS are shorter time (HR 3.5 (1.5-8.1), p = 0.001). In an analysis change clonal structure...
The emergence of treatment resistant sub-clones is a key feature relapse in multiple myeloma. Therapeutic attempts to extend remission and prevent include maximizing response the use maintenance therapy. We used whole exome sequencing study genetics paired samples taken at presentation from 56 newly diagnosed patients, following induction therapy, randomized receive either lenalidomide or observation as part Myeloma XI trial. Patients included were considered high risk, relapsing within 30...
“Just Accepted” papers have undergone full peer review and been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, proof before it is published its final version. Please note that during production of the copyedited article, errors may be discovered which could affect content. Purpose To construct evaluate performance a machine learning model bone segmentation using whole-body CT images. Materials Methods In this retrospective...
Monoclonal gammopathy of undetermined significance is a pre-malignant precursor multiple myeloma with 1% risk progression per year. Although targeted analyses have shown the presence specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS gene mutations, little known about molecular mechanism malignant transformation. We performed whole exome sequencing together comparative genomic hybridization plus single nucleotide polymorphism array analysis...