2021
Chromosomal 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 sensitivityFitnessCells
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 outcomeAneuploidy
2019
Micronuclei-based model system reveals functional consequences of chromothripsis in human cells
Kneissig M, Keuper K, de Pagter MS, van Roosmalen MJ, Martin J, Otto H, Passerini V, Sparr A, Renkens I, Kropveld F, Vasudevan A, Sheltzer JM, Kloosterman WP, Storchova Z. Micronuclei-based model system reveals functional consequences of chromothripsis in human cells. ELife 2019, 8: e50292. PMID: 31778112, PMCID: PMC6910827, DOI: 10.7554/elife.50292.Peer-Reviewed Original ResearchConceptsMassive chromosomal rearrangementsChromosomal rearrangementsHuman cellsLamin B1Replication-dependent mechanismModel systemMicronucleus sizeProper assemblyAberrant replicationChromosome shatteringChromosome transferMembrane curvatureNuclear envelopeExtra chromosomeAberrant structuresDNA damageChromosomesGrowth advantageFunctional consequencesCancer cellsAbnormal numberTrisomic cellsCellsChromosomal aberrationsRearrangement
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