Author
Jan Koster
Other affiliations: Netherlands Cancer Institute, Royal College of Surgeons in Ireland, RWTH Aachen University ...read more
Bio: Jan Koster is an academic researcher from University of Amsterdam. The author has contributed to research in topics: Neuroblastoma & Cancer. The author has an hindex of 59, co-authored 206 publications receiving 20459 citations. Previous affiliations of Jan Koster include Netherlands Cancer Institute & Royal College of Surgeons in Ireland.
Papers published on a yearly basis
Papers
More filters
••
German Cancer Research Center1, Heidelberg University2, McGill University3, Montreal Children's Hospital4, University of Düsseldorf5, University of Tübingen6, Virginia Commonwealth University7, Augsburg College8, Boston Children's Hospital9, University of Colorado Denver10, Cincinnati Children's Hospital Medical Center11, University of Würzburg12, Martin Luther University of Halle-Wittenberg13, Hannover Medical School14, Medical University of Łódź15, Memorial Hospital of South Bend16, Semmelweis University17, University of Debrecen18, University of Toronto19, University of Amsterdam20, Henry Ford Health System21, University of Texas MD Anderson Cancer Center22, University of Cambridge23
TL;DR: It is demonstrated that each H3F3A mutation defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and that they are mutually exclusive with IDH1 mutations, which characterize a third mutation-defined subgroup.
1,557 citations
••
TL;DR: Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations and may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design.
1,547 citations
••
Susanne Gröbner1, Barbara C. Worst, Joachim Weischenfeldt2, Joachim Weischenfeldt3 +182 more•Institutions (23)
TL;DR: The data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
Abstract: Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
958 citations
••
German Cancer Research Center1, University Hospital Heidelberg2, University of Toronto3, Stanford University4, University of Amsterdam5, VU University Amsterdam6, Newcastle University7, University of Bonn8, University of Hamburg9, Manchester Academic Health Science Centre10, University of Cambridge11, Karolinska Institutet12, Medical University of Vienna13, Curie Institute14, Paris Descartes University15, Harvard University16
TL;DR: A meta-analysis of all molecular and clinical data of 550 medulloblastomas brought together from seven independent studies shows how distinct the molecular subtypes are with respect to their transcriptome, DNA copy-number aberrations, demographics, and survival.
Abstract: Medulloblastoma is the most common malignant brain tumor in childhood. Molecular studies from several groups around the world demonstrated that medulloblastoma is not one disease but comprises a collection of distinct molecular subgroups. However, all these studies reported on different numbers of subgroups. The current consensus is that there are only four core subgroups, which should be termed WNT, SHH, Group 3 and Group 4. Based on this, we performed a meta-analysis of all molecular and clinical data of 550 medulloblastomas brought together from seven independent studies. All cases were analyzed by gene expression profiling and for most cases SNP or array-CGH data were available. Data are presented for all medulloblastomas together and for each subgroup separately. For validation purposes, we compared the results of this meta-analysis with another large medulloblastoma cohort (n = 402) for which subgroup information was obtained by immunohistochemistry. Results from both cohorts are highly similar and show how distinct the molecular subtypes are with respect to their transcriptome, DNA copy-number aberrations, demographics, and survival. Results from these analyses will form the basis for prospective multi-center studies and will have an impact on how the different subgroups of medulloblastoma will be treated in the future.
829 citations
••
Boston Children's Hospital1, German Cancer Research Center2, University of Texas MD Anderson Cancer Center3, St. Jude Children's Research Hospital4, University of Toronto5, Max Planck Society6, Heidelberg University7, University of Utah8, Tel Aviv University9, University of Colorado Denver10, University of Bern11, Masaryk University12, University of Texas Health Science Center at San Antonio13, University of California, San Francisco14, New York University15, University of Cambridge16, University of Hamburg17, University of Bonn18
TL;DR: The molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.
816 citations
Cited by
More filters
••
TL;DR: The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the US.
Abstract: The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control (CDC) and National Cancer Institute (NCI), is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors (malignant and non-malignant) and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates (incidence and mortality) are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 23.79 (Malignant AAAIR=7.08, non-Malignant AAAIR=16.71). This rate was higher in females compared to males (26.31 versus 21.09), Blacks compared to Whites (23.88 versus 23.83), and non-Hispanics compared to Hispanics (24.23 versus 21.48). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.5% of all tumors), and the most common non-malignant tumor was meningioma (38.3% of all tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.14. An estimated 83,830 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US in 2020 (24,970 malignant and 58,860 non-malignant). There were 81,246 deaths attributed to malignant brain and other CNS tumors between 2013 and 2017. This represents an average annual mortality rate of 4.42. The 5-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 23.5% and for a non-malignant brain and other CNS tumor was 82.4%.
9,802 citations
••
TL;DR: Some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis are highlighted, and potential therapeutic implications are discussed.
4,926 citations
••
TL;DR: The power of ComplexHeatmap is demonstrated to easily reveal patterns and correlations among multiple sources of information with four real-world datasets.
Abstract: Summary: Parallel heatmaps with carefully designed annotation graphics are powerful for efficient visualization of patterns and relationships among high dimensional genomic data. Here we present the ComplexHeatmap package that provides rich functionalities for customizing heatmaps, arranging multiple parallel heatmaps and including user-defined annotation graphics. We demonstrate the power of ComplexHeatmap to easily reveal patterns and correlations among multiple sources of information with four real-world datasets. Availability and Implementation: The ComplexHeatmap package and documentation are freely available from the Bioconductor project: http://www.bioconductor.org/packages/devel/bioc/html/ComplexHeatmap.html. Contact: m.schlesner@dkfz.de Supplementary information: Supplementary data are available at Bioinformatics online.
4,733 citations
01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
4,409 citations
••
TL;DR: It is proposed that DNA methylation age measures the cumulative effect of an epigenetic maintenance system, and can be used to address a host of questions in developmental biology, cancer and aging research.
Abstract: It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.
4,233 citations