A5091476655- Renal and related cancers
- CAR-T cell therapy research
- Acute Myeloid Leukemia Research
- Air Quality and Health Impacts
- Ethics and Legal Issues in Pediatric Healthcare
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- T-cell and Retrovirus Studies
- Birth, Development, and Health
- Chronic Myeloid Leukemia Treatments
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Acute Lymphoblastic Leukemia research
- COVID-19 impact on air quality
- Renal cell carcinoma treatment
- Neonatal Respiratory Health Research
- Single-cell and spatial transcriptomics
- Occupational and environmental lung diseases
Wellcome Sanger Institute
2023-2025
AstraZeneca (United Kingdom)
2023
University of Nebraska Medical Center
2008
Abstract In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires persistence CAR-T cells. this study, we systematically analyzed CD19 10 children with R/R B-ALL enrolled in CARPALL trial via high-throughput single-cell gene expression T sequencing infusion products serial blood bone marrow samples up to 5 years after infusion. We show that...
<p>Contains Supplementary Figures 1-9. Figure 1 shows age of diagnosis children and indel burden rearrangement for tumours from predisposed versus those with sporadic disease. 2 genomic evidence novel predispositions. 3 global methylation patterns. 4 differential gene expression. 5 mutational signatures. 6 histological subtypes across predispositions somatic drivers. 7 polyclonal clonal enrichment 11p LOH in normal kidneys. 8 phylogenies multiple neoplasms either WT1 or TRIM28 9 non...
<div>Abstract<p>Approximately 10% of children with cancer harbor a mutation in predisposition gene. In the kidney Wilms tumor, prevalence is as high 30%. Certain predispositions are associated defined histological and clinical features, suggesting differences tumorigenesis. To investigate this, we assembled cohort 137 whom 71 had pathogenic germline or mosaic variant. We examined 237 neoplasms (including two secondary leukemias), utilizing whole-genome sequencing, RNA genome-wide...
Children with Down syndrome have a 150-fold increased risk of developing myeloid leukaemia (ML-DS). Unusually for childhood leukaemia, ML-DS arises from preleukaemic state, termed transient abnormal myelopoiesis (TAM), via conserved sequence mutations. Here, we examined the relationship between genetic and transcriptional evolution natural variation; rich collection primary patient samples fetal tissues range constitutional karyotypes. We distilled consequences each step in evolution,...
Abstract Background Genetic predisposition is particularly common in children with the kidney cancer, Wilms tumor. In 10% of these children, this manifests as a family history tumor or bilateral disease. The frequency and spectrum underlying changes have not been systematically investigated. Methods We analyzed 129 suspected predisposition, 20 familial cases, 109 disease, enrolled over 30 years German SIOP93-01/GPOH SIOP2001 studies. used whole exome, genome, targeted DNA sequencing,...
Introduction: Microphysiological systems (MPS; organ-on-a-chip) aim to recapitulate the 3D organ microenvironment and improve clinical predictivity relative previous approaches. Though MPS studies provide great promise explore treatment options in a multifactorial manner, they are often very complex. It is therefore important assess manage technical confounding factors, maximise power, efficiency scalability. Methods: As an illustration of how can benefit from systematic evaluation...
Abstract Approximately 10% of children with cancer harbor a mutation in predisposition gene. In the kidney Wilms tumor, prevalence is as high 30%. Certain predispositions are associated defined histological and clinical features, suggesting differences tumorigenesis. To investigate this, we assembled cohort 137 whom 71 had pathogenic germline or mosaic variant. We examined 237 neoplasms (including two secondary leukemias), utilizing whole-genome sequencing, RNA genome-wide methylation,...
ABSTRACT Ten percent of children with cancer harbour a predisposition mutation. In the kidney cancer, Wilms tumour, prevalence is as high 30%. Certain predispositions are associated defined histological and clinical features, suggesting differences in tumour genetic development. To investigate this, we assembled cohort 137 whom 71 had pathogenic germline or mosaic predisposition. We examined 237 neoplasms (including two secondary leukaemias), utilising whole genome sequencing, RNA sequencing...
The primary function of the thyroid gland is synthesis and release hormones, which are essential for health from embryogenesis to adulthood. Thyroid disorders occur frequently include congenital hypothyroidism, occurs due aberrant development (thyroid dysgenesis) or impaired hormone particularly prevalent in trisomy 21 (T21). In contrast, carcinoma, an acquired disorder, most common endocrine malignancy both paediatric adult populations. Understanding molecular basis dysgenesis carcinoma...
Abstract Children born with Down syndrome (DS), a genetic condition caused by the presence of an additional chromosome 21 (trisomy or T21), have substantially higher risk developing childhood leukaemia. Approximately 30% DS infants develop preleukemic called transient abnormal myelopoiesis (TAM). TAM is strictly associated GATA1 truncating mutations on T21 background. Most cases spontaneously resolve within first few months life. However, age five, approximately 10% progress to...
Abstract Chimeric antigen receptor (CAR)-modified T-cells have become established as an effective treatment of haematological cancers. In the context relapsed and refractory childhood pre-B cell acute lymphoblastic leukaemia (B ALL), CD19 targeting CAR often induce durable remissions. One most critical determinants achieving a response is persistence T-cells. Here, we systematically analysed T cells ten children with or B ALL enrolled in CARPALL trial (NCT02443831). We performed high...
Abstract Ten percent of children with cancer harbor a predisposition mutation, and in the kidney cancer, Wilms tumor, prevalence may be as high 30%. Whilst clinical management known differs from that sporadic tumors, it is not dependent on type predisposition. Some predispositions are associated defined histological features, which suggests differences genetic development such tumors. To investigate this, we assembled cohort 137 whom 71 were found to have an underlying pathogenic germline or...