Joachim Weischenfeldt
A5045491737- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- Glioma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Bladder and Urothelial Cancer Treatments
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Prostate Cancer Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Genomics and Phylogenetic Studies
- Molecular Biology Techniques and Applications
- Urinary and Genital Oncology Studies
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- RNA Research and Splicing
- Lung Cancer Treatments and Mutations
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- Lymphoma Diagnosis and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- DNA Repair Mechanisms
- Cancer-related gene regulation
University of Copenhagen
2012-2025
Rigshospitalet
2012-2025
Humboldt-Universität zu Berlin
2024
Freie Universität Berlin
2024
Charité - Universitätsmedizin Berlin
2018-2024
Copenhagen University Hospital
2005-2024
European Molecular Biology Laboratory
2012-2023
Business Innovation Centre
2017-2022
European Molecular Biology Organization
2012-2022
Novo Nordisk Foundation
2022
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....
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight need molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify full spectrum of driver genes molecular processes that operate in medulloblastoma subgroups. Here we analyse somatic landscape across 491 sequenced samples heterogeneity among 1,256 epigenetically analysed cases, subgroup-specific...
INTRODUCTION Bone marrow-derived macrophages (BMM) are primary macrophage cells, derived from bone marrow cells in vitro the presence of growth factors. Macrophage colony-stimulating factor (M-CSF) is a lineage-specific that responsible for proliferation and differentiation committed myeloid progenitors into macrophage/monocyte lineage. Mice lacking functional M-CSF deficient osteoclasts suffer osteopetrosis. In this protocol, grown culture dishes M-CSF, which secreted by L929 used form...
Medulloblastoma is the most common brain tumour in children; using whole-genome sequencing of samples authors show that clinically challenging Group 3 and 4 tumours can be tetraploid, reveal expression first medulloblastoma fusion genes identified. malignant children. Four papers published 2 August 2012 issue Nature use other techniques to produce a detailed picture genetics genomics this condition. Notable findings include identification recurrent mutations not previously implicated...
Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies selected types have suggested chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium International Cancer Genome (ICGC) The Atlas (TCGA), we analyze patterns across 2,658 tumors 38 using whole-genome sequencing We find...
Structural variants (SVs), including small insertion and deletion (indels), are challenging to detect through standard alignment-based variant calling methods. Sequence assembly offers a powerful approach identifying SVs, but is difficult apply at scale genome-wide for SV detection due its computational complexity the difficulty of extracting SVs from contigs. We describe SvABA, an efficient accurate method detecting short-read sequencing data using local with low memory computing...
Abstract About half of all cancers have somatic integrations retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms retrotransposition 2,954 cancer genomes from 38 histological subtypes within framework Pan-Cancer Analysis Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired events, which affected 35% samples spanned a range event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as first...
Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma genes have not been defined and screening guidelines for genetic counselling testing paediatric patients are available. We aimed to assess define these provide evidence future guidelines.
Abstract Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes 31 and decipher their evolutionary landscape by inferring clonality the individual mutation events. Exome findings interpreted in context SNP array data from replication set 92 tumours. We identify 14 genes as main drivers, some were formerly unknown osteosarcoma. None drivers is clearly responsible for majority even...
Despite much evidence on epigenetic abnormalities in cancer, it is currently unclear to what extent alterations can be associated with tumors' clonal genetic origins. Here, we show that the prostate intratumor heterogeneity DNA methylation and copy-number patterns explained by a unified evolutionary process. By assaying multiple topographically distinct tumor sites, premalignant lesions, lymph node metastases within five cases of demonstrate both consistently reflect life history tumors....
Abstract Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as grade. To interrogate the evolutionary origins cancer heterogeneity, we analyzed 666 whole genomes. We identified a compendium 223 recurrently mutated driver regions, influencing downstream processes gene expression. validated individual germline variants that predispose tumors to acquire specific...
Nonsense-mediated mRNA decay (NMD) is a post-transcriptional surveillance process that eliminates mRNAs containing premature termination codons (PTCs). NMD has been hypothesized to impact on several aspects of cellular function; however, its importance in the context mammalian organism not addressed detail. Here we use mouse genetics demonstrate hematopoietic-specific deletion Upf2 , core factor, led rapid, complete, and lasting cell-autonomous extinction all hematopoietic stem progenitor...
A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack suitable model systems, mechanistic basis has remained elusive. We developed an integrative method termed "complex alterations after selection and transformation (CAST)," enabling efficient vitro generation complex including chromothripsis, using cell perturbations...
Nonsense-mediated mRNA decay (NMD) affects the outcome of alternative splicing by degrading isoforms with premature termination codons. Splicing regulators constitute important NMD targets; however, extent to which loss causes extensive deregulation has not previously been assayed in a global, unbiased manner. Here, we combine mouse genetics and RNA-seq provide first vivo analysis global impact on patterns two primary tissues ablated for factor UPF2.We developed bioinformatic pipeline that...
Nuclear mutations are well known to drive tumor incidence, aggression and response therapy. By contrast, the frequency roles of in maternally inherited mitochondrial genome poorly understood. Here we sequence genomes 384 localized prostate cancer patients, identify a median one single-nucleotide variant (mtSNV) per patient. Some these mtSNVs occur recurrent mutational hotspots associate with aggressive disease. Younger patients have fewer than those who diagnosed at an older age. We...
Abstract Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative lengthening associated with ATRX DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium , we dissect whole-genome sequencing data over 2500 matched tumor-control samples from 36 different tumor types aggregated within to characterize genomic footprints these mechanisms. While content tumors mutations...
Abstract Mutations in the epigenetic modifier TET2 are frequent myeloid malignancies and clonal hematopoiesis of indeterminate potential (CHIP) cytopenia undetermined significance (CCUS). Here, we investigate associations between mutations DNA methylation whole blood 305 elderly twins, 15 patients with CCUS 18 healthy controls. We find that associated hypermethylation at enhancer sites CHIP both granulocytes mononuclear cells CCUS. These hypermethylated leukocyte function immune response...
Relapsed precursor T-cell acute lymphoblastic leukemia is characterized by resistance against chemotherapy and frequently fatal. We aimed at understanding the molecular mechanisms resulting in relapse of analyzed 13 patients first diagnosis, remission whole exome sequencing, targeted ultra-deep multiplex ligation dependent probe amplification DNA methylation array. Compared to primary leukemia, number single nucleotide variants small insertions deletions approximately doubled from 11.5 26....