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 metastasisEvolving copy number gains promote tumor expansion and bolster mutational diversification
Wang Z, Xia Y, Mills L, Nikolakopoulos A, Maeser N, Dehm S, Sheltzer J, Sun R. Evolving copy number gains promote tumor expansion and bolster mutational diversification. Nature Communications 2024, 15: 2025. PMID: 38448455, PMCID: PMC10918155, DOI: 10.1038/s41467-024-46414-5.Peer-Reviewed Original ResearchConceptsSomatic copy number alterationsMutational diversificationCopy numberGenome sequenced samplesCopy number alterationsCopy number gainGenome segmentsPromote tumor expansionGenome doublingPopulation expansionSequenced samplesFitness effectsTumor typesCancer evolutionTumor expansionClonal expansionGenomeDiversification
2023
Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor
Bhattacharjee D, Bakar J, Chitnis S, Sausville E, Ashtekar K, Mendelson B, Long K, Smith J, Heppner D, Sheltzer J. Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor. Cell Chemical Biology 2023, 30: 1211-1222.e5. PMID: 37827156, PMCID: PMC10715717, DOI: 10.1016/j.chembiol.2023.09.013.Peer-Reviewed Original Research
2022
Genome-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
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
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