Featured Publications
Extrachromosomal DNA amplifications in cancer
Yi E, Chamorro González R, Henssen A, Verhaak R. Extrachromosomal DNA amplifications in cancer. Nature Reviews Genetics 2022, 23: 760-771. PMID: 35953594, PMCID: PMC9671848, DOI: 10.1038/s41576-022-00521-5.Peer-Reviewed Original ResearchConceptsExtrachromosomal DNA amplificationsNew therapeutic vulnerabilitiesCopy number heterogeneityEpigenetic architectureDNA amplificationCell divisionNuclear bodiesMost cancer typesNumber heterogeneityRegulatory landscapeTherapeutic vulnerabilitiesFunctional impactCancer typesDriver alterationsCircular structureEcDNAsChromatinizationChromosomesGenesAmplificationEcDNARecent investigationsEnhancerDeregulationCancerExtrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers
Kim H, Nguyen N, Turner K, Wu S, Gujar A, Luebeck J, Liu J, Deshpande V, Rajkumar U, Namburi S, Amin S, Yi E, Menghi F, Schulte J, Henssen A, Chang H, Beck C, Mischel P, Bafna V, Verhaak R. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nature Genetics 2020, 52: 891-897. PMID: 32807987, PMCID: PMC7484012, DOI: 10.1038/s41588-020-0678-2.Peer-Reviewed Original ResearchConceptsOncogene amplificationPoor outcomeCancer typesEcDNA amplificationShorter survivalCancer patientsMost cancer typesExtrachromosomal DNA amplificationsClinical impactMultiple cancersPatientsNormal tissuesCancerTranscript fusionsEnhanced chromatin accessibilityIntratumoral genetic heterogeneityOncogene transcriptionChromosomal amplificationOutcomesGenetic heterogeneityHigh levelsDNA amplificationTissue typesBlood
2021
Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription
Zhu Y, Gujar A, Wong C, Tjong H, Ngan C, Gong L, Chen Y, Kim H, Liu J, Li M, Mil-Homens A, Maurya R, Kuhlberg C, Sun F, Yi E, deCarvalho A, Ruan Y, Verhaak R, Wei C. Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription. Cancer Cell 2021, 39: 694-707.e7. PMID: 33836152, PMCID: PMC8119378, DOI: 10.1016/j.ccell.2021.03.006.Peer-Reviewed Original ResearchConceptsGenome-wide activationSingle-molecule resolutionMobile enhancerChromatin interactionsChromosomal interactionsChromatin contactsTranscription controlChromosomal transcriptionChromosomal targetsTranscriptional programsTranscriptional enhancersChromosomal genesChIA-PETGene transcriptionCancer genomesInteraction networksDNA functionH3K27ac signalProstate cancer cellsCircular DNAEcDNAsExpression levelsCancer cellsOncogenic alterationsTranscription
2019
Extrachromosomal oncogene amplification in tumour pathogenesis and evolution
Verhaak R, Bafna V, Mischel P. Extrachromosomal oncogene amplification in tumour pathogenesis and evolution. Nature Reviews Cancer 2019, 19: 283-288. PMID: 30872802, PMCID: PMC7168519, DOI: 10.1038/s41568-019-0128-6.Peer-Reviewed Original Research
2018
Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma
deCarvalho A, Kim H, Poisson L, Winn M, Mueller C, Cherba D, Koeman J, Seth S, Protopopov A, Felicella M, Zheng S, Multani A, Jiang Y, Zhang J, Nam D, Petricoin E, Chin L, Mikkelsen T, Verhaak R. Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma. Nature Genetics 2018, 50: 708-717. PMID: 29686388, PMCID: PMC5934307, DOI: 10.1038/s41588-018-0105-0.Peer-Reviewed Original ResearchConceptsExtrachromosomal DNA elementsDNA elementsChromosomal DNA alterationsDNA alterationsSomatic driver alterationsGenomic heterogeneitySingle nucleotide variantsOffspring cellsDiscordant inheritanceExtrachromosomal elementsEcDNAsGBM evolutionOncogenic potentialGBM samplesInheritance patternChromosomal alterationsSelection dynamicsModel systemCell culturesOrthotopic xenograft modelDriver alterationsXenograft modelOncogene amplificationCellsGlioblastoma