Arnoud Boot
A5047273273- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related gene regulation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Medical Imaging and Pathology Studies
- Occupational and environmental lung diseases
- Pancreatic and Hepatic Oncology Research
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- DNA Repair Mechanisms
- Chromatin Remodeling and Cancer
- Genomics and Chromatin Dynamics
- Glioma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Ferroptosis and cancer prognosis
- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- Evolution and Genetic Dynamics
- Sarcoma Diagnosis and Treatment
- Bladder and Urothelial Cancer Treatments
- Renal and related cancers
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
Leiden University Medical Center
2013-2024
Duke-NUS Medical School
2017-2024
GenomeScan (Netherlands)
2023-2024
University of Southern California
2012-2023
Children's Hospital of Los Angeles
2019-2023
National University of Singapore
2020-2022
Leiden University
2020
National Institutes of Health
2014
Johns Hopkins University
2011
University of Baltimore
2011
Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic signature 1 . Here, as part the Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium 2 International Cancer Genome (ICGC) and The Atlas (TCGA), we characterized signatures using 84,729,690 somatic from 4,645 whole-genome 19,184 exome sequences that encompass most types cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4...
Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II III) have highly variable clinical behavior that is not adequately predicted on basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty compounded by interobserver variability in diagnosis. Mutations IDH, TP53, ATRX codeletion chromosome arms 1p 19q (1p/19q codeletion) been implicated as clinically relevant...
Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment disease. As part The Cancer Genome Atlas project, we report here an integrated analysis 131 urothelial carcinomas to provide comprehensive landscape molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved cell-cycle regulation,...
<h2>Summary</h2> Papillary thyroid carcinoma (PTC) is the most common type of cancer. Here, we describe genomic landscape 496 PTCs. We observed a low frequency somatic alterations (relative to other carcinomas) and extended set known PTC driver include <i>EIF1AX</i>, <i>PPM1D</i>, <i>CHEK2</i> diverse gene fusions. These discoveries reduced fraction cases with unknown oncogenic from 25% 3.5%. Combined analyses variants, expression, methylation demonstrated that different groups lead...
Papillary renal-cell carcinoma, which accounts for 15 to 20% of carcinomas, is a heterogeneous disease that consists various types renal cancer, including tumors with indolent, multifocal presentation and solitary an aggressive, highly lethal phenotype. Little known about the genetic basis sporadic papillary no effective forms therapy advanced exist.We performed comprehensive molecular characterization 161 primary using whole-exome sequencing, copy-number analysis, messenger RNA microRNA...
Abstract Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters—fluke-positive (clusters 1/2) are enriched ERBB2 amplifications TP53 mutations; conversely, fluke-negative 3/4) exhibit copy-number alterations PD-1/PD-L2 or...
Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe integrated analysis somatic mutations, RNA expression, copy number, DNA methylation by The Cancer Genome Atlas a set predominantly intrahepatic CCA cases propose molecular classification scheme. We identified IDH mutant-enriched subtype distinct features including low expression chromatin modifiers, elevated mitochondrial genes, increased number....
Abstract Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining chest cavity. To expand our understanding MPM, we conducted comprehensive integrated genomic study, including most detailed analysis BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined novel subtype with TP53 SETDB1 mutations extensive loss heterozygosity. also report strong expression immune-checkpoint gene VISTA in epithelioid strikingly higher than...
Many traditional pharmacopeias include Aristolochia and related plants, which contain nephrotoxins mutagens in the form of aristolochic acids similar compounds (collectively, AA). AA is implicated multiple cancer types, sometimes with very high mutational burdens, especially upper tract urothelial cancers (UTUCs). AA-associated kidney failure UTUCs are prevalent Taiwan, but AA's role hepatocellular carcinomas (HCCs) there remains unexplored. Therefore, we sequenced whole exomes 98 HCCs from...
Highlights•Multi-omics definition of four robust molecular TET subtypes associated with survival•Thymomas have the lowest mutational burden among adult cancers•Enrichment HRAS, NRAS, TP53, and recurrent GTF2I mutations are observed•Expression autoimmune targets aneuploidy links thymoma to myasthenia gravisSummaryThymic epithelial tumors (TETs) one rarest malignancies. Among TETs, is most predominant, characterized by a unique association diseases, followed thymic carcinoma, which less common...
Cisplatin reacts with DNA and thereby likely generates a characteristic pattern of somatic mutations, called mutational signature. Despite widespread use cisplatin in cancer treatment its role contributing to secondary malignancies, signature has not been delineated. We hypothesize that cisplatin's can serve as biomarker identify mutagenesis suspected malignancies. Knowledge which tissues are at risk developing cisplatin-induced malignancies could lead guidelines for noninvasive monitoring...
ABSTRACT Somatic mutations in cancer genomes are caused by multiple mutational processes each of which generates a characteristic signature. Using 84,729,690 somatic from 4,645 whole genome and 19,184 exome sequences encompassing most types we characterised 49 single base substitution, 11 doublet four clustered 17 small insertion deletion signatures. The substantial dataset size compared to previous analyses enabled discovery new signatures, separation overlapping signatures decomposition...
Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here, we present the first whole-genome data mutational signatures of AFB1 exposure from total >40,000 mutations in four experimental systems: two different human cell lines, liver tumors wild-type mice, mice carried hepatitis B surface antigen transgene-this to model multiplicative effects aflatoxin causing HCC. all systems were remarkably...
Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information multiomic sequencing, NanoString immuno-oncology profiling, multiplex immunohistochemistry immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head neck exhibited higher tumor mutation burden (TMB) UV mutational signatures; others were mutationally...
Topoisomerases nick and reseal DNA to relieve torsional stress associated with transcription replication resolve structures such as knots catenanes. Stabilization of the yeast Top2 cleavage intermediates is mutagenic in yeast, but whether this extends higher eukaryotes less clear. Chemotherapeutic topoisomerase poisons also elevate cleavage, resulting mutagenesis. Here, we describe p.K743N mutations human hTOP2α link them a previously undescribed mutator phenotype cancer. Overexpression...
Colibactin, a genotoxin produced by polyketide synthase harboring (pks