2025
MIF as an oncogenic driver of low‐heterogeneity melanomas
Tran T, Sánchez‐Zuno G, Kulkarni R, Kluger H, Bucala R. MIF as an oncogenic driver of low‐heterogeneity melanomas. Molecular Oncology 2025, 19: 1295-1298. PMID: 40131169, PMCID: PMC12077282, DOI: 10.1002/1878-0261.70031.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorImproving therapeutic outcomesMigration inhibitory factorPotential therapeutic utilityImmune landscapeMelanoma clonesImmune escapeT cellsImmunoregulatory cytokinesTumor heterogeneityTumor progressionOncogenic driversPathway inhibitorTherapeutic outcomesTumor evolutionInhibitory factorCell proliferationMelanomaTumorCellsAntagonistCytokines
2024
Passenger gene co-amplifications create collateral therapeutic vulnerabilities in cancer
Bei Y, Bramé L, Kirchner M, Fritsche-Guenther R, Kunz S, Bhattacharya A, Rusu M, Gürgen D, Dubios F, Köppke J, Proba J, Wittstruck N, Sidorova O, González R, Garcia H, Brückner L, Xu R, Giurgiu M, Rodriguez-Fos E, Yu Q, Spanjaard B, Koche R, Schmitt C, Schulte J, Eggert A, Haase K, Kirwan J, Hagemann A, Mertins P, Dörr J, Henssen A. Passenger gene co-amplifications create collateral therapeutic vulnerabilities in cancer. Cancer Discovery 2024, 14: 492-507. PMID: 38197697, PMCID: PMC10911929, DOI: 10.1158/2159-8290.cd-23-1189.Peer-Reviewed Original ResearchMeSH KeywordsCell DeathHumansMechanistic Target of Rapamycin Complex 1Medical OncologyNeoplasmsOncogenesConceptsDEAD-box helicase 1Passenger genesTherapeutic vulnerabilitiesTricarboxylic acidCRISPR-Cas9 loss-of-function screensLoss-of-function screensCell death in vitroDisruption of mTORC1Death in vitroGene co-amplificationCancer cell linesCancer genomesHelicase 1Interaction partnersCancer dependenciesCollateral vulnerabilitiesTCA activityCo-amplificationDNA amplificationMTORC1 activityCancerPharmacological disruptionCancer biologyTarget discoveryCoamplificationDefining the Role of Extrachromosomal DNA Amplifications in Medulloblastoma.
Zhao D, Verhaak R. Defining the Role of Extrachromosomal DNA Amplifications in Medulloblastoma. Cancer Research 2024, 84: 515-516. PMID: 38175761, DOI: 10.1158/0008-5472.can-23-4025.Peer-Reviewed Original ResearchConceptsCell-to-cell variabilityWhole-genome sequencingCircular extrachromosomal DNACRISPRi experimentsRewiring eventsExtrachromosomal DNAMultiomics sequencingExtrachromosomal DNA amplificationsCopy numberEcDNADNA amplificationAssociated with worse survivalOncogene amplificationSequenceAmplificationWorse survivalPatient cohortTumor heterogeneityIntratumoral heterogeneityCRISPRiMedulloblastomaPatient outcomesDNA
2023
Oncogenic context shapes the fitness landscape of tumor suppression
Blair L, Juan J, Sebastian L, Tran V, Nie W, Wall G, Gerceker M, Lai I, Apilado E, Grenot G, Amar D, Foggetti G, Do Carmo M, Ugur Z, Deng D, Chenchik A, Paz Zafra M, Dow L, Politi K, MacQuitty J, Petrov D, Winslow M, Rosen M, Winters I. Oncogenic context shapes the fitness landscape of tumor suppression. Nature Communications 2023, 14: 6422. PMID: 37828026, PMCID: PMC10570323, DOI: 10.1038/s41467-023-42156-y.Peer-Reviewed Original ResearchOncogene-like addiction to aneuploidy in human cancers
Girish V, Lakhani A, Thompson S, Scaduto C, Brown L, Hagenson R, Sausville E, Mendelson B, Kandikuppa P, Lukow D, Yuan M, Stevens E, Lee S, Schukken K, Akalu S, Vasudevan A, Zou C, Salovska B, Li W, Smith J, Taylor A, Martienssen R, Liu Y, Sun R, Sheltzer J. Oncogene-like addiction to aneuploidy in human cancers. Science 2023, 381: eadg4521. PMID: 37410869, PMCID: PMC10753973, DOI: 10.1126/science.adg4521.Peer-Reviewed Original ResearchParallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells
Chamorro González R, Conrad T, Stöber M, Xu R, Giurgiu M, Rodriguez-Fos E, Kasack K, Brückner L, van Leen E, Helmsauer K, Dorado Garcia H, Stefanova M, Hung K, Bei Y, Schmelz K, Lodrini M, Mundlos S, Chang H, Deubzer H, Sauer S, Eggert A, Schulte J, Schwarz R, Haase K, Koche R, Henssen A. Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells. Nature Genetics 2023, 55: 880-890. PMID: 37142849, PMCID: PMC10181933, DOI: 10.1038/s41588-023-01386-y.Peer-Reviewed Original ResearchConceptsExtrachromosomal circular DNACircular DNAParallel sequencingCancer cellsIntercellular differencesFull-length mRNADNA elementsExtrachromosomal DNATranscriptome sequencingTranscriptional impactSingle cancer cellsEcDNAExpression differencesDNATranscriptomeCellsIntratumoral heterogeneityStructural heterogeneitySequenceStructural dynamicsMRNACancerRecombinationEpigenomic charting and functional annotation of risk loci in renal cell carcinoma
Nassar A, Abou Alaiwi S, Baca S, Adib E, Corona R, Seo J, Fonseca M, Spisak S, El Zarif T, Tisza V, Braun D, Du H, He M, Flaifel A, Alchoueiry M, Denize T, Matar S, Acosta A, Shukla S, Hou Y, Steinharter J, Bouchard G, Berchuck J, O’Connor E, Bell C, Nuzzo P, Mary Lee G, Signoretti S, Hirsch M, Pomerantz M, Henske E, Gusev A, Lawrenson K, Choueiri T, Kwiatkowski D, Freedman M. Epigenomic charting and functional annotation of risk loci in renal cell carcinoma. Nature Communications 2023, 14: 346. PMID: 36681680, PMCID: PMC9867739, DOI: 10.1038/s41467-023-35833-5.Peer-Reviewed Original ResearchConceptsMaster transcription factorChIP-seqATAC-seq dataH3K27ac ChIP-seqCcRCC cell linesEpigenomic atlasATAC-seqFunctional annotationTranscriptional landscapePrimary human samplesTranscription factorsRNA-seqRisk lociTranscriptional upregulationSNP arrayRisk SNPsETS-1EpigenomeCell linesFOXI1Renal cell carcinomaEPAS1RCC histologic subtypesHuman samplesBHLHE41
2022
Developmental Deconvolution for Classification of Cancer Origin
Moiso E, Farahani A, Marble H, Hendricks A, Mildrum S, Levine S, Lennerz J, Garg S. Developmental Deconvolution for Classification of Cancer Origin. Cancer Discovery 2022, 12: 2566-2585. PMID: 36041084, PMCID: PMC9627133, DOI: 10.1158/2159-8290.cd-21-1443.Peer-Reviewed Original ResearchYES1 Is a Druggable Oncogenic Target in SCLC
Redin E, Garrido-Martin EM, Valencia K, Redrado M, Solorzano JL, Carias R, Echepare M, Exposito F, Serrano D, Ferrer I, Nunez-Buiza A, Garmendia I, García-Pedrero JM, Gurpide A, Paz-Ares L, Politi K, Montuenga LM, Calvo A. YES1 Is a Druggable Oncogenic Target in SCLC. Journal Of Thoracic Oncology 2022, 17: 1387-1403. PMID: 35988891, DOI: 10.1016/j.jtho.2022.08.002.Peer-Reviewed Original ResearchConceptsSubpopulation of patientsOncogenic targetsPatient-derived xenograftsMarked antitumor activityGain/amplificationPlasma-derived exosomesDistant metastasisIndependent predictorsTargetable oncogenesPoor prognosisAggressive subtypeClinical managementLung cancerPharmacologic blockadeTumor regressionMouse modelTumor growthPlasma exosomesMolecular subgroupsPharmacologic inhibitionMetastasisAntitumor activityFunctional experimentsOrganoid modelsClinical samplesExtrachromosomal 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 investigationsEnhancerDeregulationCancerAttribution of Cancer Origins to Endogenous, Exogenous, and Preventable Mutational Processes
Cannataro VL, Mandell JD, Townsend JP. Attribution of Cancer Origins to Endogenous, Exogenous, and Preventable Mutational Processes. Molecular Biology And Evolution 2022, 39: msac084. PMID: 35580068, PMCID: PMC9113445, DOI: 10.1093/molbev/msac084.Peer-Reviewed Original ResearchConceptsBurden of cancerPublic health strategiesWhole-exome sequencingTobacco exposureLung cancerProstate adenocarcinomaBreast cancerCancer effectsHealth strategiesOncogenic driversCancer originCancer typesCancer cell lineagesCancerPathogen exposureExogenous mutational processesMajority of mutationsTumorsSingle nucleotide variantsPreventable processActivity accountsSurvivalOncogenic variantsCell lineagesProliferationEpigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer
Wang C, Leavenworth J, Zhang C, Liu Z, Yuan K, Wang Y, Zhang G, Wang S, Cui X, Zhang Y, Bae S, Zhou J, Wang L, Liu R. Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer. Oncogene 2022, 41: 2778-2785. PMID: 35361883, PMCID: PMC9215223, DOI: 10.1038/s41388-022-02272-3.Peer-Reviewed Original ResearchConceptsCpG-rich islandDNA methylationProstate cancer cellsEpigenetic regulationPrimary prostate cancerProstate cancerTargets of DNA methylationCancer cellsCRISPR-Cas9-based toolHuman prostate cancer cellsOncogenic roleCancer cell proliferation in vitroProstate cancer in vitroTranslational regulationOncogenic translationProtein translationUntranslated regionTumor growth in vivoNormal prostate tissueRNA sequencingCell proliferation in vitroCancer in vitroEIF4A1Growth in vivoElevated mRNA levelsGenome-wide identification and analysis of prognostic features in human cancers
Smith JC, Sheltzer JM. Genome-wide identification and analysis of prognostic features in human cancers. Cell Reports 2022, 38: 110569. PMID: 35354049, PMCID: PMC9042322, DOI: 10.1016/j.celrep.2022.110569.Peer-Reviewed Original ResearchConceptsAdverse biomarkersSignificant prognostic biomarkerShorter survival timePromising therapeutic targetPatient survival dataPreclinical cancer researchPrognostic featuresAggressive malignancyClinical trialsPatient outcomesPatient riskPrognostic biomarkerSurvival timeTherapeutic targetSuccessful drug targetsClinical decisionCancerSurvival dataTherapeutic developmentHuman cancersBiomarkersBiomarker analysisDriver genesCancer researchCancer driver genesIntegrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis
Farshidfar F, Rhrissorrakrai K, Levovitz C, Peng C, Knight J, Bacchiocchi A, Su J, Yin M, Sznol M, Ariyan S, Clune J, Olino K, Parida L, Nikolaus J, Zhang M, Zhao S, Wang Y, Huang G, Wan M, Li X, Cao J, Yan Q, Chen X, Newman AM, Halaban R. Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis. Nature Communications 2022, 13: 898. PMID: 35197475, PMCID: PMC8866401, DOI: 10.1038/s41467-022-28566-4.Peer-Reviewed Original ResearchConceptsAcral melanomaMelanoma subtypesClinical profilingCommon melanoma subtypeImmune checkpoint blockadeCheckpoint blockadeInferior survivalMelanoma cell linesKey molecular driversPoor prognosisTherapeutic targetAnchorage-independent growthImmunomodulatory genesNon-white individualsHotspot mutationsMolecular driversCandidate oncogeneMelanomaApoptotic cell deathLZTR1Focal amplificationTumor promoterCell linesMetastasisTumor suppressor
2021
Targeting STAT3 prevents bile reflux‐induced oncogenic molecular events linked to hypopharyngeal carcinogenesis
Vageli DP, Doukas PG, Siametis A, Judson BL. Targeting STAT3 prevents bile reflux‐induced oncogenic molecular events linked to hypopharyngeal carcinogenesis. Journal Of Cellular And Molecular Medicine 2021, 26: 75-87. PMID: 34850540, PMCID: PMC8742186, DOI: 10.1111/jcmm.17011.Peer-Reviewed Original ResearchConceptsBcl-2 overexpressionTranscriptional activationTranscription factorsTranscriptional activitySignal transducerSTAT3 knockdownMolecular eventsCell survivalQPCR analysisLuciferase assaySTAT3 activationTargeting STAT3Oncogenic eventsAberrant activationHypopharyngeal carcinogenesisSTAT3 phosphorylationSTAT3Oncogenic effectsSTAT3 pathwayPharmacologic inhibitionPharmacological inhibitionSTA-21Hypopharyngeal cellsOncogenic profileWestern blotPIK3CA mutation in a case of CTNNB1 mutant sinonasal glomangiopericytoma
Hong C, Khan M, Sukys J, Prasad M, Erson-Omay EZ, Vining E, Omay SB. PIK3CA mutation in a case of CTNNB1 mutant sinonasal glomangiopericytoma. Molecular Case Studies 2021, 8: mcs.a006120. PMID: 34667073, PMCID: PMC8744496, DOI: 10.1101/mcs.a006120.Peer-Reviewed Original ResearchMeSH KeywordsAgedbeta CateninClass I Phosphatidylinositol 3-KinasesFemaleGlomus TumorHumansMutationOncogenesConceptsCase of glomangiopericytomaWhole-exome sequencingInstitutional review board-approved protocolTargeted medical therapyUnderwent surgical resectionPI3K/Akt/mTORWnt/β-cateninAkt/mTORPrimary sinonasal tumorSurgical resectionClinicopathologic characteristicsMedical therapyRare tumorPIK3CA mutationsSinonasal tumorsGlomangiopericytomaTumorsΒ-cateninSomatic mutationsComprehensive genetic characterizationGenomic characterizationMutationsConcurrent dysregulationResectionSinonasalIntegrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer
Sheng T, Ho S, Ooi W, Xu C, Xing M, Padmanabhan N, Huang K, Ma L, Ray M, Guo Y, Sim N, Anene-Nzelu C, Chang M, Razavi-Mohseni M, Beer M, Foo R, Sundar R, Chan Y, Tan A, Ong X, Skanderup A, White K, Jha S, Tan P. Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer. Genome Medicine 2021, 13: 158. PMID: 34635154, PMCID: PMC8504099, DOI: 10.1186/s13073-021-00970-3.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationADP-Ribosylation FactorsCell Line, TumorCell ProliferationChromatinEnhancer Elements, GeneticEpigenomicsGene Expression Regulation, NeoplasticGenomicsHistonesHumansInhibitor of Growth Protein 1OncogenesPromoter Regions, GeneticRNA-SeqStomach NeoplasmsTranscriptomeWhole Genome SequencingConceptsSingle nucleotide polymorphismsActivity-by-contactEnhancer-promoter interactionsSomatic copy number alterationsGermline single nucleotide polymorphismsHistone modificationsDistal cis-regulatory elementsLow somatic mutation rateCell-specific gene expressionCis-regulatory elementsFunctional enhancer activityHistone modification profilesWhole-genome sequencingRegulatory region sequencingCell fate determinationSuper-enhancer regionsCopy number alterationsGenome copy numberEffect of histone acetylationSomatic mutation rateCancer-relevant genesFunctional assay dataEnhanced activityGC cell linesRegion sequencesIntegrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity
Park J, Daniels J, Wartewig T, Ringbloom KG, Martinez-Escala ME, Choi S, Thomas JJ, Doukas PG, Yang J, Snowden C, Law C, Lee Y, Lee K, Zhang Y, Conran C, Tegtmeyer K, Mo SH, Pease DR, Jothishankar B, Kwok PY, Abdulla FR, Pro B, Louissaint A, Boggon T, Sosman J, Guitart J, Rao D, Ruland J, Choi J. Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity. Blood 2021, 138: 1225-1236. PMID: 34115827, PMCID: PMC8499046, DOI: 10.1182/blood.2020009655.Peer-Reviewed Original ResearchConceptsPutative driver genesDriver genesCutaneous T-cell lymphomaDisease phenotypePutative tumor suppressorT-cell lymphomaMycosis fungoidesDiverse disease phenotypesPutative genetic causesSezary syndromeDNA/RNA sequencingGenomic analysisRNA sequencingMolecular basisTumor suppressorDisease stageStructural variantsGenetic relationshipsTranscriptional signatureGenesDisease heterogeneityFunctional assaysNovel insightsSkin-homing T cellsLeukemic diseaseThe Clonal Expansion Dynamics of the HIV-1 Reservoir: Mechanisms of Integration Site-Dependent Proliferation and HIV-1 Persistence
Yeh YJ, Yang K, Razmi A, Ho YC. The Clonal Expansion Dynamics of the HIV-1 Reservoir: Mechanisms of Integration Site-Dependent Proliferation and HIV-1 Persistence. Viruses 2021, 13: 1858. PMID: 34578439, PMCID: PMC8473165, DOI: 10.3390/v13091858.Peer-Reviewed Original ResearchConceptsHIV-1-infected cellsHIV-1 latent reservoirAntiretroviral therapyHIV-1Cancer-related gene expressionHIV-1 promoterHIV-1 integration sitesLatent reservoirClonal expansionClonal expansion dynamicsCancer-related genesLong-term suppressive antiretroviral therapyHIV-1 promoter activitySuppressive antiretroviral therapyLow-level viremiaHIV-1 reservoirHIV-1 persistenceHIV-1 transcriptionCertain cancer-related genesViral reboundGene expressionRare caseLoss of functionTherapeutic agentsTumor suppressor geneOncogenic 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
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