A5044647886- Renal and related cancers
- Renal cell carcinoma treatment
- Tumors and Oncological Cases
- Ethics and Legal Issues in Pediatric Healthcare
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Childhood Cancer Survivors' Quality of Life
- Pluripotent Stem Cells Research
- Cancer-related gene regulation
- Congenital Anomalies and Fetal Surgery
- Acute Lymphoblastic Leukemia research
- Bioinformatics and Genomic Networks
- Galectins and Cancer Biology
- Genetic and Kidney Cyst Diseases
- Protein Tyrosine Phosphatases
- Viral Infections and Immunology Research
- Gene Regulatory Network Analysis
- interferon and immune responses
- Virus-based gene therapy research
- Retinoids in leukemia and cellular processes
- Genomics and Chromatin Dynamics
- Tuberous Sclerosis Complex Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Genomic variations and chromosomal abnormalities
- Prenatal Screening and Diagnostics
University of Würzburg
2010-2025
Comprehensive Cancer Center Mainfranken
2015-2025
Cardio-Pulmonary Institute
2024
Justus-Liebig-Universität Gießen
2024
Universities of Giessen and Marburg Lung Center
2024
German Center for Lung Research
2024
Cardiff University
2010-2016
University College London
2010-2016
University Hospital of Wales
2016
University Hospital Heidelberg
2016
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into biology. Here we present comprehensive analysis of genetic alterations in pan-cancer cohort including 961 tumours from children, adolescents, young adults, comprising 24 distinct molecular cancer. Using standardized workflow, identified marked terms mutation frequency significantly mutated genes comparison previously analysed adult cancers....
Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols based on staging and histologic assessment response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, successfully treated are exposed treatments with significant risks late effects. To investigate whether molecular biomarkers could improve stratification, we assessed 1q...
Soft tissue tumors of infancy encompass an overlapping spectrum diseases that pose unique diagnostic and clinical challenges. We studied genomes transcriptomes cryptogenic congenital mesoblastic nephroma (CMN), extended our findings to five anatomically or histologically related soft tumors: infantile fibrosarcoma (IFS), nephroblastomatosis, Wilms tumor, malignant rhabdoid clear cell sarcoma the kidney. A key finding is recurrent mutation EGFR in CMN by internal tandem duplication kinase...
// Richard D. Williams 1 , Tasnim Chagtai Marisa Alcaide-German John Apps Jenny Wegert 2 Sergey Popov 3 Gordan Vujanic 4 Harm van Tinteren 5 Marry M. den Heuvel-Eibrink 6 Marcel Kool 7 Jan de Kraker 8 David Gisselsson 9 Norbert Graf 10 Manfred Gessler and Kathy Pritchard-Jones UCL Institute of Child Health, London, UK Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry Comprehensive Cancer Center Mainfranken, Wuerzburg University, Wuerzburg, Germany Research, Sutton, Surrey,...
Wilms' tumor (WT), the most common pediatric renal malignancy, is associated with mutations in several well-characterized genes, notably WT1, CTNNB1, WTX, and TP53. However, majority of cases do not harbor these genes. We hypothesized that additional drivers behavior would be contained within areas consistent genomic copy number change, especially those WT risk groups defined by International Society Paediatric Oncology (SIOP).We analyzed high-resolution (Affymetrix 250K single nucleotide...
TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, alterations reported no more than 60% of anaplastic tumours, recent data suggested their presence tumours that do not fulfil the criteria anaplasia, questioning clinical utility analysis. Therefore, we characterized status 84 cases irrespective histological subtype. We identified at least 90% even when diffuse was present, indicating very strong if...
Two percent of patients with Wilms tumors have a positive family history. In many these cases the genetic cause remains unresolved. By applying germline exome sequencing in two families affected individuals tumors, we identified truncating mutations TRIM28 . Subsequent mutational screening and tumor DNA 269 children by was performed, revealed seven additional mutations, one individual somatic mutation TRIM28. encodes complex scaffold protein involved different processes, including gene...
Abstract Wilms tumor (WT) is one of the most common solid tumors in childhood. Mutations WT1 and CTNNB1 are well established as causal alterations about 10–15% cases. Recently, WTX (WT gene on X‐chromosome), a implicated WNT signaling, has been identified third WT gene. We determined mutation status , large set 429 tumors. Genomic were 17% WTs, equally distributed between males females. Analysis 104 samples for point mutations revealed rate only 2%. An additional 11.5% lacked expression...
Current treatment protocols for Wilms tumor achieve 90% cure rates, but relapse risk and side effects from therapy remain challenging. Over the last decade, numerous markers have been proposed classification and/or prediction of outcome. However, cohort sizes were quite variable often small. We now provide a large-scale reassessment by real-time RT-PCR 40 in 102 tumors followed validation potentially relevant an independent set 74 tumors. In first data set, individual comparison with...
Abstract Purpose: Wilms' tumor is a childhood cancer of the kidney with an incidence ∼1 in 10,000. Cooccurrence 2q37 deletion syndrome, uncommon constitutional chromosome abnormality, has been reported previously three children. Given these are independently rare clinical entities, we hypothesized that harbors suppressor gene important pathogenesis. Experimental Design: To test this, performed loss heterozygosity analysis panel 226 sporadic samples and mutation candidate genes. Results: Loss...
Recent research elucidated the prognostic significance of molecular biology in Wilms tumor (WT) by linking somatic genomic variants (such as gain chromosome 1q) to unfavorable patient outcomes. This analysis describes clinical impact copy number variations (CNV) samples WT patients with stage IV disease. Tumor 55 disease from United Kingdom, France, and Germany enrolled SIOP 2001 study treated preoperative chemotherapy (pCHT) were examined for their CNVs 1q other regions interest using...
<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...
<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...
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,...
Wilms tumor (WT) is the most common renal in childhood. Among others, MYCN copy number gain and P44L MAX R60Q mutations have been identified WT. encodes a transcription factor that requires dimerization with to activate of numerous target genes. has associated adverse prognosis different childhood tumors including The mutations, located either transactivating or basic helix-loop-helix domain, respectively, are predicted be damaging by pathogenicity prediction tools, but functional...
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 In vitro models represent a critical tool in cancer research to study tumor biology and evaluate new treatment options. Unfortunately, there are no effective preclinical available that Wilms (WT) — the most common pediatric renal tumor. Especially high-risk blastemal WT subtype is not represented by few primary cell lines established until now. Here, we describe 3D approach for cultivation of cells, where cultures grown suspension as spheroids could be propagated long-term. Besides...
Abstract Functional analysis of gene candidates and testing novel therapeutics in Wilms tumors (WT) has been hampered by the lack vitro model systems. WT are characterized a spectrum histological appearances, but published cell lines mostly derived from rare anaplastic variants or even non‐WT. There some success establishing primary cultures, these often poorly only less frequent WT1 mutant tumors. We report generation set WT‐cell cultures using simple cultivation protocol. Our could be...
Abstract Wilms tumors (WTs) are histologically diverse childhood cancers with variable contributions of blastema, stroma, and epithelia. A variety cancer genes operate in WTs, including the tripartite‐motif‐containing‐28 gene ( TRIM28 ). Case reports small case series suggest that mutations associated epithelial morphology WT predisposition. Here, we systematically investigated prevalence inactivation predisposing a cohort 126 WTs >2/3 cells, spanning 20 years biobanking German...