ArticleOncoscience2015
Whole genome sequence analysis links chromothripsis to EGFR, MDM2, MDM4, and CDK4 amplification in glioblastoma.
Article in Oncoscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 60 citations in OpenAlex.
- Chromosomal Instability Drives Glioblastoma Heterogeneity and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Unrevealing the dual role of paired box and sex determining region Y related high mobility group box in glioblastoma.Discover oncology · 2026Review
- Comprehensive ceRNA Profiling Uncovers Clinically Relevant Hub lncRNAs in Glioblastoma.Bioinformatics and biology insights · 2026Article
- Genomic landscape of diffuse glioma revealed by whole genome sequencing.Nature communications · 2025Article
- Cancer cells' chamber of secrets: the link between micronuclei, chromothripsis and malignancy.Open biology · 2025Review
- Therapy enhancing chromosome instability may be advantageous forNAR cancer · 2025Article
- Machine Learning for Detecting and Analyzing Chromoanagenesis Events.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Whole-genome doubling is a double-edged sword: the heterogeneous role of whole-genome doubling in various cancer types.BMB reports · 2024Review
- A Retrospective Genomic Landscape of 661 Young Adult Glioblastomas Diagnosed Using 2016 WHO Guidelines for Central Nervous System Tumors.The oncologist · 2024Article
- Insights into brain tumor diagnosis: exploringFrontiers in neurology · 2024Review
- Comprehensive Molecular Genetic Analysis in Glioma Patients by Next Generation Sequencing.Brain tumor research and treatment · 2024Article
- Pan-cancer analysis of chromothripsis-related gene expression patterns indicates an association with tumor immune and therapeutic agent responses.Frontiers in oncology · 2023Article
- Unravelling the tumour genome: The evolutionary and clinical impacts of structural variants in tumourigenesis.The Journal of pathology · 2022Review
- Phasing analysis of lung cancer genomes using a long read sequencer.Nature communications · 2022Article
- Canine Oral Melanoma Genomic and Transcriptomic Study Defines Two Molecular Subgroups with Different Therapeutical Targets.Cancers · 2022Article
- Chromoanagenesis Landscape in 10,000 TCGA Patients.Cancers · 2021Article
- Chromothripsis-Explosion in Genetic Science.Cells · 2021Review
- Epidemiology of Anthropometric Factors in Glioblastoma Multiforme-Literature Review.Brain sciences · 2021Review
- RNA-sequencing of IDH-wild-type glioblastoma with chromothripsis identifies novel gene fusions with potential oncogenic properties.Translational oncology · 2021Article
- DNA CpG methylation in sequential glioblastoma specimens.Journal of cancer research and clinical oncology · 2020Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFindings based on recent advances in next-generation sequence analysis suggest that, in some tumors, a single catastrophic event, termed chromothripsis, results in several simultaneous tumorigenic alterations. Previous studies have suggested that glioblastoma (GBM) may exhibit chromothripsis at a higher rate (39%) than other tumors (9%). Primary glioblastoma is an aggressive form of brain cancer that typically appears suddenly in older adults. With aggressive treatment, the median survival time is only 15 months. Their acute onset and widespread genomic instability indicates that chromothripsis may play a key role in their initiation and progression. GBMs are often characterized by EGFR amplification, CDKN2A and PTEN deletion, although approximately 20% of GBMs harbor additional amplifications in MDM2 or MDM4 with CDK4.
methodsWe used the chromothripsis prediction tool, Shatterproof, in conjunction with a custom whole genome sequence analysis pipeline in order to generate putative regions of chromothripsis. The data derived from this study was further expanded on using fluorescence in situ hybridization (FISH) analysis and susceptibility studies with colony formation assays.
resultsWe show that primary GBMs are associated with higher chromothripsis scores and establish a link between chromothripsis and gene amplification of receptor tyrosine kinases (RTKs), as well as modulators of the TP53 and RB1 pathways.
conclusionsUtilizing a newly introduced bioinformatic tool, we provide evidence that chromothripsis is associated with the formation of amplicons containing several oncogenes involved in key pathways that are likely essential for post-chromothriptic cell survival.
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