2023
More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome
Minteer C, Thrush K, Gonzalez J, Niimi P, Rozenblit M, Rozowsky J, Liu J, Frank M, McCabe T, Sehgal R, Higgins-Chen A, Hofstatter E, Pusztai L, Beckman K, Gerstein M, Levine M. More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome. Science Advances 2023, 9: eadf4163. PMID: 37467337, PMCID: PMC10355820, DOI: 10.1126/sciadv.adf4163.Peer-Reviewed Original ResearchConceptsStem cell divisionImmortalized human cellsTissue-specific cancer riskTumorigenic stateCell divisionDNA methylationEpigenetic changesAge-related accumulationHuman cellsMultiple tissuesSomatic mutationsClinical tissuesTissue differencesEpigenomeCellsTissueNormal tissuesMethylationMutationsReplicationNormal breast tissueSignaturesVitroAccumulationDivision
2020
Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden
Qing T, Mohsen H, Marczyk M, Ye Y, O’Meara T, Zhao H, Townsend JP, Gerstein M, Hatzis C, Kluger Y, Pusztai L. Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden. Nature Communications 2020, 11: 2438. PMID: 32415133, PMCID: PMC7228928, DOI: 10.1038/s41467-020-16293-7.Peer-Reviewed Original ResearchConceptsAge groupsGermline variantsSomatic mutationsLate-onset cancerEarly-onset cancersCancer hallmark genesSomatic mutation burdenMutation burdenMalignant transformationCancer genesYounger ageGermline alterationsCancerVariant burdenBurdenAverage numberHallmark genesAgeNegative correlationStrong negative correlationMutationsPatientsGroup
2017
Functional germline variants as potential co-oncogenes
Agarwal D, Nowak C, Zhang NR, Pusztai L, Hatzis C. Functional germline variants as potential co-oncogenes. Npj Breast Cancer 2017, 3: 46. PMID: 29177190, PMCID: PMC5700137, DOI: 10.1038/s41523-017-0051-5.Peer-Reviewed Original ResearchRecent genome sequencing studiesFunction of proteinsDifferent oncogenic eventsGermline variantsGenome sequencing studiesSomatic mutationsDriver mutationsPhenotypic variationSpecific cancer subtypesLarge breast cancer cohortSomatic driver mutationsSequencing studiesFull malignant transformationFunctional germline variantsCancer biologyRecurrent driver mutationsOncogenic eventsSomatic eventsMutationsGermline aberrationsGermline polymorphismsFamilial cancerIndividual cancersMalignant transformationPolymorphismStructural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer
Chen C, Gu P, Wu J, Chen X, Niu S, Sun H, Wu L, Li N, Peng J, Shi S, Fan C, Huang M, Wong CC, Gong Q, Kumar-Sinha C, Zhang R, Pusztai L, Rai R, Chang S, Lei M. Structural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer. Nature Communications 2017, 8: 14929. PMID: 28393832, PMCID: PMC5394241, DOI: 10.1038/ncomms14929.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsConserved SequenceDNA DamageDNA Mutational AnalysisDNA RepairGenomic InstabilityHumansMiceModels, MolecularMolecular ChaperonesMutationNeoplasmsPhosphoproteinsProstaglandin-E SynthasesProtein BindingProtein Structure, SecondaryScattering, Small AngleShelterin ComplexStructure-Activity RelationshipTelomere-Binding ProteinsX-Ray DiffractionConceptsTelomerase-mediated telomere extensionHuman cancersDNA damage responseC-terminal mutationsOB foldsHuman POT1Chromosome endsGenome instabilityPOT1-TPP1Telomere extensionDamage responseStable heterodimerA-NHEJStructural insightsC-terminusInappropriate repairTPP1POT1Heart-shaped structureMissense mutationsTerminal portionMutationsDomainMutantsTelomeres
2016
Deciphering and Targeting Oncogenic Mutations and Pathways in Breast Cancer
Santarpia L, Bottai G, Kelly CM, Győrffy B, Székely B, Pusztai L. Deciphering and Targeting Oncogenic Mutations and Pathways in Breast Cancer. The Oncologist 2016, 21: 1063-1078. PMID: 27384237, PMCID: PMC5016060, DOI: 10.1634/theoncologist.2015-0369.Peer-Reviewed Original ResearchConceptsBreast cancerCancer-causing genesCopy number variationsRNA speciesRNA editingGenomic variationNext-generation sequencingRNA sequencingGenomic complexityGenomic portraitGreater genomic complexityOncogenic mutationsOncogenic eventsTarget profilingRare mutationsMutationsRecurrent mutationsSomatic variantsGenetic aberrationsFormal clinical trialsPotential therapeutic implicationsDriver mutationsSequencingGermline variantsMolecular abnormalities
2015
A genome-wide approach to link genotype to clinical outcome by utilizing next generation sequencing and gene chip data of 6,697 breast cancer patients
Pongor L, Kormos M, Hatzis C, Pusztai L, Szabó A, Győrffy B. A genome-wide approach to link genotype to clinical outcome by utilizing next generation sequencing and gene chip data of 6,697 breast cancer patients. Genome Medicine 2015, 7: 104. PMID: 26474971, PMCID: PMC4609150, DOI: 10.1186/s13073-015-0228-1.Peer-Reviewed Original ResearchConceptsRNA-seq dataNext-generation sequencingBreast cancer patientsTranscriptomic fingerprintGenome-wide approachesGeneration sequencingClinical outcomesCancer patientsHuman gene mutationsTumor suppressor geneGene chip dataSuch genesRNA-seqGene mutationsLarge breast cancer cohortGene expressionChip dataSuppressor geneBreast cancer cohortGenesMicroarray dataMutationsSomatic mutationsClinical characteristicsCox regression
2013
Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing
Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, Schnall-Levin M, White J, Sanford EM, An P, Sun J, Juhn F, Brennan K, Iwanik K, Maillet A, Buell J, White E, Zhao M, Balasubramanian S, Terzic S, Richards T, Banning V, Garcia L, Mahoney K, Zwirko Z, Donahue A, Beltran H, Mosquera JM, Rubin MA, Dogan S, Hedvat CV, Berger MF, Pusztai L, Lechner M, Boshoff C, Jarosz M, Vietz C, Parker A, Miller VA, Ross JS, Curran J, Cronin MT, Stephens PJ, Lipson D, Yelensky R. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nature Biotechnology 2013, 31: 1023-1031. PMID: 24142049, PMCID: PMC5710001, DOI: 10.1038/nbt.2696.Peer-Reviewed Original Research