Kerstin Haase
A5081872336- Cancer Genomics and Diagnostics
- Neuroblastoma Research and Treatments
- CRISPR and Genetic Engineering
- Genetics, Bioinformatics, and Biomedical Research
- Epigenetics and DNA Methylation
- Advanced Breast Cancer Therapies
- Cancer therapeutics and mechanisms
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- DNA Repair Mechanisms
- Science, Research, and Medicine
- Evolution and Genetic Dynamics
- Genetic factors in colorectal cancer
- PARP inhibition in cancer therapy
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genomics and Chromatin Dynamics
- RNA Interference and Gene Delivery
- Chromosomal and Genetic Variations
- Advanced biosensing and bioanalysis techniques
- Microtubule and mitosis dynamics
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- Bioinformatics and Genomic Networks
- Molecular Biology Techniques and Applications
University College London
2023-2025
London Cancer
2025
Cancer Research UK
2025
CRUK Lung Cancer Centre of Excellence
2025
The Francis Crick Institute
2016-2024
Charité - Universitätsmedizin Berlin
2019-2024
German Cancer Research Center
2021-2024
Heidelberg University
2021-2024
Max Delbrück Center
2020-2023
Freie Universität Berlin
2021-2023
Cancer develops as a result of somatic mutation and clonal selection, but quantitative measures selection in cancer evolution are lacking. We adapted methods from molecular applied them to 7,664 tumors across 29 types. Unlike species evolution, positive outweighs negative during development. On average, <1 coding base substitution/tumor is lost through with purifying almost absent outside homozygous loss essential genes. This allows exome-wide enumeration all driver mutations, including...
Tobacco smoking increases the risk of at least 17 classes human cancer. We analyzed somatic mutations and DNA methylation in 5243 cancers types for which tobacco confers an elevated risk. Smoking is associated with increased mutation burdens multiple distinct mutational signatures, contribute to different extents cancers. One these mainly found derived from tissues directly exposed smoke, attributable misreplication damage caused by carcinogens. Others likely reflect indirect activation...
Cancer develops through a process of somatic evolution
Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, drivers ITH across cancer types are poorly understood. To address this, we extensively characterize whole-genome sequences 2,658 samples spanning 38 types. Nearly all informative (95.1%) contain evidence distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection driver mutations most...
Abstract Gains and losses of DNA are prevalent in cancer emerge as a consequence inter-related processes replication stress, mitotic errors, spindle multipolarity breakage–fusion–bridge cycles, among others, which may lead to chromosomal instability aneuploidy 1,2 . These copy number alterations contribute initiation, progression therapeutic resistance 3–5 Here we present conceptual framework examine the patterns human that is widely applicable diverse data types, including whole-genome...
Abstract Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study osteosarcoma to date, comprising 112 childhood adult tumours encompassing all major histological subtypes. A key finding our identification mutations in insulin-like growth factor (IGF) signalling genes 8/112 (7%) cases. We validate this observation using fluorescence situ hybridization (FISH) an additional 87 osteosarcomas, with IGF1 receptor ( IGF1R )...
Abstract MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA (ecDNA). exact amplicon structure has not been described thus far and the functional relevance its rearrangements is unknown. Here, we analyze using short-read Nanopore sequencing chromatin landscape ChIP-seq, ATAC-seq Hi-C. This reveals two distinct classes amplicons which explain regulatory requirements for...
Abstract Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution provide information for the complex task of phylogenetic inference. We present MEDICC2, a method inferring evolutionary trees WGD using haplotype-specific alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as infinite sites assumption, allowing multiple mutations parallel evolution, does not treat adjacent loci...
Abstract Extrachromosomal DNAs (ecDNAs) are common in cancer, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity still unresolved. Here we describe single-cell extrachromosomal circular DNA transcriptome sequencing (scEC&T-seq), a method for parallel of full-length mRNA from single cells. By applying scEC&T-seq to cancer cells, intercellular differences ecDNA content while investigating transcriptional impact. Oncogene-containing ecDNAs...
Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one the highest burdens structural aberrations across human cancer. Here, we sought to unravel molecular basis complexity in by integrating DNA sequencing, ploidy analysis, gene expression, methylation profiling. We identified whole genome duplication as a prevalent pernicious force USARC tumorigenesis. Using mathematical...
Abstract Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of cancers using 194 patients from Nigeria 1037 The Cancer Genome Atlas (TCGA). Relative Black White cohorts TCGA, Nigerian HR + /HER2 − tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, greater structural...
Abstract Intratumour heterogeneity is a major cause of treatment failure in cancer. We present in-depth analyses combining transcriptomic and genomic profiling with ultra-deep targeted sequencing multiregional biopsies 10 patients neuroblastoma, devastating childhood tumour. observe high spatial temporal somatic mutations copy-number alterations which are reflected on the level. Mutations some druggable target genes including ALK FGFR1 heterogeneous at diagnosis and/or relapse, raising issue...
ABSTRACT Tobacco smoking increases the risk of at least 15 classes cancer. We analyzed somatic mutations and DNA methylation in 5,243 cancers types for which tobacco confers an elevated risk. Smoking is associated with increased mutation burdens multiple distinct mutational signatures, contribute to different extents cancers. One these mainly found derived from tissues directly exposed smoke, attributable misreplication damage caused by carcinogens. Others likely reflect indirect activation...
Abstract Most cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive oncogenesis. Here, using multiplatform sequencing technologies, we identify and characterize a remarkable mutational mechanism in human hepatocellular carcinoma caused Hepatitis B virus, which DNA molecules from virus inserted into genome causing dramatic changes its configuration, including non-homologous chromosomal fusions, dicentric chromosomes...
DNA amplifications in cancer do not only harbor oncogenes. We sought to determine whether passenger coamplifications could create collateral therapeutic vulnerabilities. Through an analysis of >3,000 genomes followed by the interrogation CRISPR-Cas9 loss-of-function screens across >700 cell lines, we determined that are accompanied distinct dependency profiles. In a proof-of-principle study, demonstrate coamplification bona fide gene DEAD-Box Helicase 1 (DDX1) creates increased on mTOR...
Mouse substrains genetically transmitting the exogenous Moloney murine leukemia virus (Mo-MuLV) at a single locus have been derived previously by infection of preimplantation embryos. Here we explore potential retroviral vectors for transferring nonviral genes into germ line mice. Preimplantation mouse embryos were cocultivated with cell that produces recombinant retrovirus whose genome carries Escherichia coli gene gpt. We show vector sequence was inserted embryo and frequency similar to...
Summary Cancer develops through a process of somatic evolution. Here, we use whole-genome sequencing 2,778 tumour samples from 2,658 donors to reconstruct the life history, evolution mutational processes, and driver mutation sequences 39 cancer types. The early phases oncogenesis are driven by point mutations in small set genes, often including biallelic inactivation suppressors. Early is also characterised specific copy number gains, such as trisomy 7 glioblastoma or isochromosome 17q...
Abstract We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines allele frequencies both SV breakends, then simultaneously estimates and copy number. assess performance using in silico mixtures real samples, at known proportions, created two clonal metastases same patient. find that SVclone’s is comparable to single-nucleotide variant-based methods, despite having...
Abstract The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types co-occur in the same tumours. However, it remains unclear how processes change during evolution due to lack reliable methods reconstruct evolutionary trajectories mutational signature activity. Here, as part ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data from 2658...
Circular extrachromosomal DNA (ecDNA) is a form of oncogene amplification found across cancer types and associated with poor outcome in patients. ecDNA can be structurally complex contain rearranged sequences derived from multiple chromosome locations. As the structure impact regulation may indicate mechanisms its formation, disentangling it at high resolution sequencing data essential. Even though methods have been developed to identify reconstruct genome sequencing, remains challenging...