2023
Aneuploidy in human cancer: new tools and perspectives
Lakhani A, Thompson S, Sheltzer J. Aneuploidy in human cancer: new tools and perspectives. Trends In Genetics 2023, 39: 968-980. PMID: 37778926, PMCID: PMC10715718, DOI: 10.1016/j.tig.2023.09.002.Peer-Reviewed Original ResearchConceptsSpecific chromosomal changesClinical prognosisConsequences of aneuploidyTreatment strategiesFeature of cancerIsogenic cell linesDosage-sensitive genesShort palindromic repeatsCancer developmentCopy number imbalancesMalignant growthHuman cancersAneuploid chromosomesCell linesPalindromic repeatsCancerChromosomal changesAneuploidyNumber imbalancesPrognosis
2022
Extensive protein dosage compensation in aneuploid human cancers
Schukken KM, Sheltzer J. Extensive protein dosage compensation in aneuploid human cancers. Genome Research 2022, 32: 1254-1270. PMID: 35701073, PMCID: PMC9341510, DOI: 10.1101/gr.276378.121.Peer-Reviewed Original ResearchConceptsDosage compensationPost-translational regulatory mechanismsProtein complex subunitsCopy numberHuman cancersCell cycle genesEffects of aneuploidyMajority of proteinsChromosome copy numberProtein expression dataKey driver genesChromosome copy number changesExpression of oncogenesCopy number changesKey cancer driversComplex subunitsCycle genesGene groupsCancer driversCancer proteomeRegulatory mechanismsTumor suppressorExpression dataDriver genesChromosome gains
2021
Chromosomal instability and aneuploidy as causes of cancer drug resistance
Lukow DA, Sheltzer JM. Chromosomal instability and aneuploidy as causes of cancer drug resistance. Trends In Cancer 2021, 8: 43-53. PMID: 34593353, DOI: 10.1016/j.trecan.2021.09.002.Peer-Reviewed Original ResearchConceptsChromosomal instabilityGene dosage alterationsChromosome copy number changesCopy number changesCell fitnessCancer drug resistanceCellular adaptabilitySelective pressureDrug resistanceTumor evolutionNumber changesDosage alterationsRecent evidenceAneuploidyIntratumoral heterogeneityPoor patient outcomesFitnessHigh levelsUnique vulnerabilitiesResistanceChromosomal instability accelerates the evolution of resistance to anti-cancer therapies
Lukow DA, Sausville EL, Suri P, Chunduri NK, Wieland A, Leu J, Smith JC, Girish V, Kumar AA, Kendall J, Wang Z, Storchova Z, Sheltzer JM. Chromosomal instability accelerates the evolution of resistance to anti-cancer therapies. Developmental Cell 2021, 56: 2427-2439.e4. PMID: 34352222, PMCID: PMC8933054, DOI: 10.1016/j.devcel.2021.07.009.Peer-Reviewed Original ResearchConceptsChromosomal instabilityAnti-cancer therapyCancer cell fitnessAcquisition of aneuploidyChromosome loss eventsSingle-cell sequencingEvolution of resistanceDifferent culture environmentsCellular fitnessPhenotypic plasticityCIN correlatesHuman tumorsCell fitnessHuman cellsStressful environmentsResistant populationsAcquisition of resistanceRecurrent aneuploidyCancer cellsPaclitaxel-resistant cellsCulture environmentAneuploidyPaclitaxel sensitivityFitnessCellsAneuploidy as a promoter and suppressor of malignant growth
Vasudevan A, Schukken KM, Sausville EL, Girish V, Adebambo OA, Sheltzer JM. Aneuploidy as a promoter and suppressor of malignant growth. Nature Reviews Cancer 2021, 21: 89-103. PMID: 33432169, DOI: 10.1038/s41568-020-00321-1.Peer-Reviewed Original Research
2020
Aneuploidy increases resistance to chemotherapeutics by antagonizing cell division
Replogle JM, Zhou W, Amaro AE, McFarland JM, Villalobos-Ortiz M, Ryan J, Letai A, Yilmaz O, Sheltzer J, Lippard SJ, Ben-David U, Amon A. Aneuploidy increases resistance to chemotherapeutics by antagonizing cell division. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 30566-30576. PMID: 33203674, PMCID: PMC7720170, DOI: 10.1073/pnas.2009506117.Peer-Reviewed Original ResearchConceptsCell cycle delayG1 cell cycle delayChromosome gainsSingle chromosome gainsCycle delayWhole chromosome gainsCancer Cell Line Encyclopedia (CCLE) datasetsDrug resistanceCell divisionCellular stressEuploid cellsPoor disease outcomeG1 delayPoor patient prognosisS phaseSelective benefitsSlow proliferationChemotherapeutic cisplatinChemotherapeutic resistanceCancer cellsSlowed proliferationChemotherapy treatmentPatient prognosisDisease outcomeAneuploidySingle-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer
Vasudevan A, Baruah PS, Smith JC, Wang Z, Sayles NM, Andrews P, Kendall J, Leu J, Chunduri NK, Levy D, Wigler M, Storchová Z, Sheltzer JM. Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer. Developmental Cell 2020, 52: 413-428.e6. PMID: 32097652, PMCID: PMC7354079, DOI: 10.1016/j.devcel.2020.01.034.Peer-Reviewed Original ResearchMeSH KeywordsAneuploidyAnimalsApoptosisCell MovementCell ProliferationChromosomal InstabilityChromosomes, Human, Pair 5Colonic NeoplasmsEpithelial-Mesenchymal TransitionFemaleHumansMaleMembrane ProteinsMiceMice, NudeNeoplasm InvasivenessNucleotidyltransferasesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsSingle extra chromosomeCell state transitionsCGAS/STING signalingCell linesCopy number dataPartial epithelial-mesenchymal transitionCancer aneuploidyPhenotypic plasticityGenomic plasticitySingle chromosomeEpithelial-mesenchymal transitionMetastasis suppressorChromosomal instabilityExtra chromosomeCertain aneuploidiesDifferent aneuploidiesCancer progressionSpecific aneuploidiesChromosomal gainsChromosomesSTING signalingMetastatic behaviorTumor progressionAneuploidyUniform driver
2018
Systematic identification of mutations and copy number alterations associated with cancer patient prognosis
Smith J, Sheltzer J. Systematic identification of mutations and copy number alterations associated with cancer patient prognosis. ELife 2018, 7: e39217. PMID: 30526857, PMCID: PMC6289580, DOI: 10.7554/elife.39217.Peer-Reviewed Original ResearchConceptsPatient prognosisSuccessful treatment decisionsDriver genesIndependent patient cohortsRobust prognostic biomarkerCancer patient prognosisSignificant prognostic powerSpecific therapeutic vulnerabilitiesSpecific cancer typesPatient cohortWorse outcomesDeadly malignancyPatient riskClinical riskPrognostic biomarkerTreatment decisionsPrognostic powerMolecular alterationsTherapeutic vulnerabilitiesCopy number alterationsCancer typesFocal CNAsTotal aneuploidyGenomic profilesPrognosis
2017
Single-chromosome Gains Commonly Function as Tumor Suppressors
Sheltzer J, Ko J, Replogle J, Burgos N, Chung E, Meehl C, Sayles N, Passerini V, Storchova Z, Amon A. Single-chromosome Gains Commonly Function as Tumor Suppressors. Cancer Cell 2017, 31: 240-255. PMID: 28089890, PMCID: PMC5713901, DOI: 10.1016/j.ccell.2016.12.004.Peer-Reviewed Original ResearchConceptsSingle chromosome gainsSingle extra chromosomeEffects of aneuploidyHallmarks of cancerEvolutionary flexibilityFitness defectsEuploid cellsTumor suppressorExtra chromosomeEuploid counterpartsOncogenic pathwaysProlonged growthChromosomal alterationsCancer developmentCell linesTrisomic cellsImproved fitnessAneuploidyTrisomic cell lineCellsChromosomesSuppressorAdditional chromosomal alterationsGrowthTumorigenesis
2013
A Transcriptional and Metabolic Signature of Primary Aneuploidy Is Present in Chromosomally Unstable Cancer Cells and Informs Clinical Prognosis
Sheltzer J. A Transcriptional and Metabolic Signature of Primary Aneuploidy Is Present in Chromosomally Unstable Cancer Cells and Informs Clinical Prognosis. Cancer Research 2013, 73: 6401-6412. PMID: 24041940, PMCID: PMC3901577, DOI: 10.1158/0008-5472.can-13-0749.Peer-Reviewed Original ResearchConceptsChromosomal instabilityPrimary cellsUnstable cancer cellsAneuploid cellsSubset of genesProliferation-independent mannerHigh mitotic activityCancer cell linesAggressive diseasePoor prognosisClinical prognosisTypes of aneuploidyPrimary aneuploidyCellular stressAbnormal karyotypeTranscriptional alterationsHuman patientsTCA cycle fluxCancerMetabolic signaturesAneuploid cancersTranscriptional signatureCancer cellsCancer linesMitotic activity
2012
Transcriptional consequences of aneuploidy
Sheltzer J, Torres E, Dunham M, Amon A. Transcriptional consequences of aneuploidy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 12644-12649. PMID: 22802626, PMCID: PMC3411958, DOI: 10.1073/pnas.1209227109.Peer-Reviewed Original ResearchConceptsConsequences of aneuploidyRelated gene expression patternsAneuploid cellsSimilar cellular pathwaysGene expression patternsGene expression dataDiverse organismsDifferent organismsTranscriptional consequencesDifferent chromosomesCell physiologyCellular pathwaysExpression patternsGene expressionCell cycleExpression dataDifferent aneuploidiesAntiproliferative responseCell proliferationGenesOrganismsSpeciesAneuploidySpecific chromosomal aberrationsChromosomal aberrations
2011
The aneuploidy paradox: costs and benefits of an incorrect karyotype
Sheltzer J, Amon A. The aneuploidy paradox: costs and benefits of an incorrect karyotype. Trends In Genetics 2011, 27: 446-453. PMID: 21872963, PMCID: PMC3197822, DOI: 10.1016/j.tig.2011.07.003.Peer-Reviewed Original ResearchConceptsCell proliferationRole of aneuploidyHallmarks of cancerExperimental evolutionEnhanced proliferative capacityCellular phenotypesChromosomal instabilityAneuploid cellsNormal cellsKaryotypic imbalancesProliferative capacityAneuploidyDiverse effectsProliferationCellsPhenotypeMicroorganismsKaryotypeHallmarkAneuploidy Drives Genomic Instability in Yeast
Sheltzer J, Blank H, Pfau S, Tange Y, George B, Humpton T, Brito I, Hiraoka Y, Niwa O, Amon A. Aneuploidy Drives Genomic Instability in Yeast. Science 2011, 333: 1026-1030. PMID: 21852501, PMCID: PMC3278960, DOI: 10.1126/science.1206412.Peer-Reviewed Original ResearchMeSH KeywordsAneuploidyChromosome SegregationChromosomes, FungalDNA DamageDNA RepairDNA ReplicationDNA, FungalGenome, FungalGenomic InstabilityMutagenesisMutationNeoplasmsPhenotypeRad52 DNA Repair and Recombination ProteinRecombination, GeneticSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsConceptsGenomic instabilityMitotic recombinationDefective DNA damage repairEffects of aneuploidyDNA damage repairCellular fitnessFission yeastGenomic stabilitySingle chromosomeEnhanced proliferative capacityChromosome lossDamage repairExtra copiesYeastGenetic alterationsProliferative capacityAneuploidyMost strainsMalignant growthRecombinationChromosomesTumorigenesisFitnessCopiesGrowth