Featured Publications
Oncogene-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 Research
2024
An elevated rate of whole-genome duplications in cancers from Black patients
Brown L, Hagenson R, Koklič T, Urbančič I, Qiao L, Strancar J, Sheltzer J. An elevated rate of whole-genome duplications in cancers from Black patients. Nature Communications 2024, 15: 8218. PMID: 39300140, PMCID: PMC11413164, DOI: 10.1038/s41467-024-52554-5.Peer-Reviewed Original ResearchConceptsWhole-genome duplicationRate of whole-genome duplicationsBlack patientsSelf-reported Black patientsChromosomal copy number changesRates of cancer mortalityCopy number changesInfluence racial disparitiesAssociated with environmental exposuresCancer mortalityGenomic eventsAssociated with shorter patient survivalCancer outcomesRacial disparitiesGenomic alterationsShorter patient survivalBlack individualsWhite patientsEnvironmental exposuresRacial groupsCell culturesAggressive diseasePatient survivalLung cancerEnhanced metastasis
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 gainsGenome-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 genes
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
Discovering and validating cancer genetic dependencies: approaches and pitfalls
Lin A, Sheltzer JM. Discovering and validating cancer genetic dependencies: approaches and pitfalls. Nature Reviews Genetics 2020, 21: 671-682. PMID: 32561862, DOI: 10.1038/s41576-020-0247-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsDrug Delivery SystemsGenetic TechniquesGenomicsHumansNeoplasms
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 profilesPrognosisMELK expression correlates with tumor mitotic activity but is not required for cancer growth
Giuliano C, Lin A, Smith J, Palladino A, Sheltzer J. MELK expression correlates with tumor mitotic activity but is not required for cancer growth. ELife 2018, 7: e32838. PMID: 29417930, PMCID: PMC5805410, DOI: 10.7554/elife.32838.Peer-Reviewed Original ResearchConceptsMaternal embryonic leucine zipper kinaseTumor mitotic activityCancer typesMitotic activityPoor clinical prognosisBreast cancer cell linesPromising therapeutic targetTriple-negative breast cancer cell linesEmbryonic leucine zipper kinaseMultiple cancer typesLeucine zipper kinaseCancer cell linesCytotoxic chemotherapyAggressive diseaseCancer patientsClinical prognosisMELK expressionTherapeutic targetChemotherapy resistanceCancer growthTumor growthAcute inhibitionMELK inhibitorExpression correlatesCancer-related processes
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
2011
Aneuploidy 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