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
2022
Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer
Yi E, Gujar A, Guthrie M, Kim H, Zhao D, Johnson K, Amin S, Costa M, Yu Q, Das S, Jillette N, Clow P, Cheng A, Verhaak R. Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer. Cancer Discovery 2022, 12: 468-483. PMID: 34819316, PMCID: PMC8831456, DOI: 10.1158/2159-8290.cd-21-1376.Peer-Reviewed Original ResearchConceptsExtrachromosomal DNA elementsDNA elementsUneven segregationRNA polymerase IILive-cell imagingPolymerase IIOffspring cellsGene transcriptionCell line modelsEcDNAsRandom segregationGenetic materialLiving cellsCopy numberLive cellsIndividual cellsTumor evolutionMitosisInheritance patternBreakpoint sequencesIssue featureTranscriptionFluorescent markersPatient tissuesCells
2021
Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer
Kocakavuk E, Anderson K, Varn F, Johnson K, Amin S, Sulman E, Lolkema M, Barthel F, Verhaak R. Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer. Nature Genetics 2021, 53: 1088-1096. PMID: 34045764, PMCID: PMC8483261, DOI: 10.1038/s41588-021-00874-3.Peer-Reviewed Original ResearchConceptsWorse clinical outcomesNon-irradiated tumorsClinical outcomesRecurrent cancerPatient survivalPoor outcomeMetastatic tumorsRecurrent gliomaRadiation therapyRadiation-induced DNA damageDNA damageGlioma Longitudinal Analysis ConsortiumMutational signature analysisCancer treatmentDeletion burdenRadiotherapyMedical FoundationAPOBEC mutagenesisSignificant increaseTumorsCancerDNA damage repairDeletion signatureMutational spectrumSmall deletions
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
2017
TumorFusions: an integrative resource for cancer-associated transcript fusions
Hu X, Wang Q, Tang M, Barthel F, Amin S, Yoshihara K, Lang F, Martinez-Ledesma E, Lee S, Zheng S, Verhaak R. TumorFusions: an integrative resource for cancer-associated transcript fusions. Nucleic Acids Research 2017, 46: gkx1018-. PMID: 29099951, PMCID: PMC5753333, DOI: 10.1093/nar/gkx1018.Peer-Reviewed Original ResearchConceptsTranscript fusionsGene fusionsWhole-genome sequencing dataSomatic DNA rearrangementsTranscript-level expressionGenome sequencing dataGene annotationCopy number levelsCancer samplesCancer Genome AtlasDNA rearrangementsUniform pipelineFunctional fusionSequencing dataIntegrative resourceLevel expressionPartner genesGenome AtlasChromosomal alterationsMutational patternsCancer typesFusion transcriptsNon-neoplastic samplesMolecular aberrationsNumber levels