Uwe Kordes
A5059945643- Glioma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Cancer Mechanisms and Therapy
- Neuroblastoma Research and Treatments
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Hedgehog Signaling Pathway Studies
- Gestational Trophoblastic Disease Studies
- Protein Degradation and Inhibitors
- Ocular Oncology and Treatments
- Cancer-related Molecular Pathways
- Meningioma and schwannoma management
- Mechanisms of cancer metastasis
- RNA modifications and cancer
- interferon and immune responses
- Childhood Cancer Survivors' Quality of Life
- Neurofibromatosis and Schwannoma Cases
- Sarcoma Diagnosis and Treatment
- Blood groups and transfusion
- Peptidase Inhibition and Analysis
- Renal and related cancers
- Neuroendocrine Tumor Research Advances
- Soft tissue tumor case studies
- Genomics and Chromatin Dynamics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
Universität Hamburg
2016-2025
University Medical Center Hamburg-Eppendorf
2016-2025
Klinik und Poliklinik für Kinder- und Jugendmedizin
2002-2023
Society of Paediatric Oncology and Haematology
2021
Eppendorf (Germany)
2017
German Cancer Research Center
2016
Goethe University Frankfurt
2016
University Hospital Heidelberg
2016
University Hospital Münster
2009-2016
University of Tübingen
2016
Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years age, and carried out histologic review, methylation profiling, custom panel, genome, or exome sequencing. After excluding tumors representing other established entities subgroups, we identified 130 to be part an "intrinsic" spectrum disease specific infant...
The large diversity of central nervous system (CNS) tumor types in children and adolescents results disparate patient outcomes renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling targeted gene panel sequencing with blinded neuropathological reference diagnostics for a population-based cohort more than 1,200 newly diagnosed pediatric patients CNS tumors, to assess their utility routine neuropathology. We show that the multi-omic...
Background: Intracranial choroid plexus tumors (CPT) are rare and primarily affect young children. Leptomeningeal dissemination (LMD) has been reported not only in high-grade carcinoma (CPC) but also lower histological grades; however, a systematic evaluation of CPT-specific imaging characteristics remains lacking. Methods: We analyzed the LMD single-center pediatric cohort 22 CPT patients (thirteen papilloma (CPP), six atypical (aCPP), three CPC), comparing features with those primary...
Abstract Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignant pediatric brain characterized by genetic alterations affecting the SMARCB1 ( hSNF5/INI1 ) locus in chromosome band 22q11.2. To identify potential additional alterations, high‐resolution genome‐wide analysis was performed using molecular inversion probe single‐nucleotide polymorphism (MIP SNP) assay (Affymetrix OncoScan formalin‐fixed paraffin‐embedded express) on DNA isolated from 18 archival samples. Alterations could be...
Abstract Background Controversy exists as to what may be defined standard of care (including markers for stratification) patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated and offers standardized genetic DNA methylation analyses. Methods Clinical, genetic, treatment data 143 from 13 countries were analyzed (2009–2017). Therapy consisted surgery, anthracycline-based induction, either radiotherapy or high dose...
PURPOSE BRAF V600 mutation is detected in 5%-10% of pediatric high-grade gliomas (pHGGs), and effective treatments are limited. In previous trials, dabrafenib as monotherapy or combination with trametinib demonstrated activity children adults relapsed/refractory V600–mutant HGG. METHODS This phase II study evaluated plus patients pHGG. The primary objective was overall response rate (ORR) by independent review Response Assessment Neuro-Oncology criteria. Secondary objectives included ORR...
Abstract The SMARCB1 gene status in 50 patients with atypical teratoid rhabdoid tumor and/or malignant recruited to a German registry was prospectively analyzed FISH and PCR. Altogether we found 40 mutations 28 patients. Two were positive for staining at immunochemistry. Germline identified 10 of 41 CNS disease, including three large heterozygous deletions, six truncating one donor splice site mutation. No missense mutation identified. Analysis first degree relatives did not detect any...
Atypical teratoid/rhabdoid tumors are malignant embryonal characterized by the presence of rhabdoid cells, genetic alterations affecting SMARCB1 gene (hSNF5/INI1), and a poor prognosis. Whether INI1 plays role in pathogenesis other central nervous system is uncertain. We report on cases 2 young children with unusual intracranial nonrhabdoid neuroectodermal within around third or fourth ventricle that cribriform strands trabeculae well-defined epithelial membrane antigen-immunopositive...
Choroid plexus tumors are intraventricular neoplasms derived from the choroid epithelium. A better knowledge of molecular factors involved in tumor biology may aid identifying patients at risk for recurrence. Methylation profiles were examined 29 papillomas (CPPs, WHO grade I), 32 atypical (aCPPs, II), and 31 carcinomas (CPCs, III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP aCPP...
Abstract Atypical teratoid/rhabdoid tumors (ATRTs) are very aggressive childhood malignancies of the central nervous system. The underlying genetic cause inactivating bi-allelic mutations in SMARCB1 or (rarely) SMARCA4. ATRT-SMARCA4 have been associated with a higher frequency germline mutations, younger age, and an inferior prognosis comparison to mutated cases. Based on their DNA methylation profiles transcriptomics, ATRTs divided into three distinct molecular subgroups: ATRT-TYR,...
Choroid plexus tumors (CPTs) are intraventricular brain predominantly arising in children but also affecting adults. In most cases, driver mutations have not been identified, although there reports of frequent chromosome-wide copy-number alterations and TP53 mutations, especially choroid carcinomas (CPCs).DNA methylation profiling RNA-sequencing was performed a series 47 CPTs. Samples comprised 35 papillomas (CPPs), 6 atypical (aCPPs) CPCs plus three recurrences thereof. Targeted TERT...
The rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, liver central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 due pathogenic variants (PV) in genes encoding constituents BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) SMARCA4 (RTPS2). In contrast other disorders related PVs such...
Abstract Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT–TYR, ATRT–MYC ATRT–SHH. ATRT–SHH represents the largest group heterogeneous with regard to age, location epigenetic profile. We, therefore, aimed investigate if heterogeneity within might also have biological clinical importance. Consensus clustering DNA methylation profiles confirmatory t-SNE...
Abstract BACKGROUND. Ovarian small cell carcinoma of the hypercalcemic type is a rare neoplasm that associated with poor prognosis. The objective current study was to investigate clinicopathologic features this tumor and develop preliminary diagnostic therapeutic guidelines. METHODS. Between 1994 2005, 11 girls (ages 9–22 years) who were registered on German Maligne Keimzelltumoren studies Kiel Pediatric Tumor Registry analyzed. Prior histopathologic review, 8 patients had been misdiagnosed...
Choroid plexus carcinoma is a malignant brain tumor predominantly occurring in young children. Only limited data are available regarding the underlying molecular genetic alterations. Therefore, inversion probe single nucleotide polymorphism (MIP SNP) arrays were performed on series of 26 neuropathologically well‐characterized choroid carcinomas. Recurrent copy number losses chromosomes 5, 6, 16, 18, 19, and 22 as well gains 1, 2, 4, 12, 20 identified. Furthermore, GISTIC analysis identified...
Rhabdoid tumor predisposition syndrome is usually associated with shorter survival in patients malignant rhabdoid tumors regardless of anatomical origin. Here we present four children harboring truncating heterozygous SMARCB1/INI1 germline mutations favorable outcome. All received multi-modality treatment, three according to therapeutic recommendations by the EU-RHAB registry, two without radiotherapy, and mean event-free accounts for 7 years. In conclusion, intensive treatment curative...