2021
Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial.
Venet D, Rediti M, Maetens M, Fumagalli D, Brown DN, Majjaj S, Salgado R, Pusztai L, Harbeck N, El-Abed S, Wang Y, Saura C, Gomez H, Semiglazov VF, de Azambuja E, Huober J, Nuciforo P, Di Cosimo S, Piccart M, Loi S, Rothé F, Sotiriou C. Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial. Clinical Cancer Research 2021, 27: clincanres.1317.2021. PMID: 34321278, DOI: 10.1158/1078-0432.ccr-21-1317.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDNA Copy Number VariationsFemaleHumansNeoadjuvant TherapyNeoplasm Recurrence, LocalReceptor, ErbB-2TrastuzumabConceptsPathologic complete responseNeoALTTO trialCopy number aberrationsBreast cancerHER2-positive early-stage breast cancerEstrogen receptor-positive subgroupNeoadjuvant anti-HER2 therapyEarly-stage breast cancerHER2-positive breast cancerPhase III clinical trialsAnti-HER2 therapyAnti-HER2 agentsPredictors of responseReceptor-positive subgroupNumber aberration analysisCopy number levelsWarrants further investigationHeterogeneity of responseComplete responseSurvival outcomesWhole cohortClinical trialsImmune processesPatientsSignificant associationWhole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers
Li X, Kumar S, Harmanci A, Li S, Kitchen RR, Zhang Y, Wali VB, Reddy SM, Woodward WA, Reuben JM, Rozowsky J, Hatzis C, Ueno NT, Krishnamurthy S, Pusztai L, Gerstein M. Whole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers. Genome Medicine 2021, 13: 70. PMID: 33902690, PMCID: PMC8077918, DOI: 10.1186/s13073-021-00879-x.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsWhole-genome sequencingGermline single nucleotide variantsInternational Cancer Genome ConsortiumGenomic featuresGenomic alterationsGenome ConsortiumClonal architectureWhole Genomes (PCAWG) ConsortiumNon-coding regionsCancer-related pathwaysNon-IBC samplesCancer Genome Atlas ProgramMAST2 geneCopy number profilesPan-cancer analysisTGF-β pathwayGenomic architectureGenomic regionsSimilar genomic alterationsSimilar genomic characteristicsComplex SVsIBC samplesGenomic differencesOverall mutational load
2017
Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations
Brown D, Smeets D, Székely B, Larsimont D, Szász AM, Adnet PY, Rothé F, Rouas G, Nagy ZI, Faragó Z, Tőkés AM, Dank M, Szentmártoni G, Udvarhelyi N, Zoppoli G, Pusztai L, Piccart M, Kulka J, Lambrechts D, Sotiriou C, Desmedt C. Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations. Nature Communications 2017, 8: 14944. PMID: 28429735, PMCID: PMC5474888, DOI: 10.1038/ncomms14944.Peer-Reviewed Original ResearchConceptsDistant metastasisPrimary tumorClonal frequency analysisMultiple metastatic lesionsBreast cancer disseminationBreast cancer progressionSomatic mutationsWhole-exome sequencingAvailable metastasesMetastatic lesionsMetastatic precursorsPrimary lesionMetastatic tumorsDisease progressionBreast cancerPatterns of disseminationMetastasisMetastatic progressionCancer disseminationPatientsCancer progressionCopy number profilingCopy number aberrationsTumorsMonoclonal origin
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 ResearchMeSH KeywordsBreast NeoplasmsDNA Copy Number VariationsFemaleGenome, HumanGenotypeHigh-Throughput Nucleotide SequencingHumansMutationOligonucleotide Array Sequence AnalysisSequence Analysis, RNAConceptsRNA-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
2014
Statistical measures of transcriptional diversity capture genomic heterogeneity of cancer
Jiang T, Shi W, Natowicz R, Ononye SN, Wali VB, Kluger Y, Pusztai L, Hatzis C. Statistical measures of transcriptional diversity capture genomic heterogeneity of cancer. BMC Genomics 2014, 15: 876. PMID: 25294321, PMCID: PMC4197225, DOI: 10.1186/1471-2164-15-876.Peer-Reviewed Original ResearchCombined analysis of gene expression, DNA copy number, and mutation profiling data to display biological process anomalies in individual breast cancers
Shi W, Balazs B, Györffy B, Jiang T, Symmans WF, Hatzis C, Pusztai L. Combined analysis of gene expression, DNA copy number, and mutation profiling data to display biological process anomalies in individual breast cancers. Breast Cancer Research And Treatment 2014, 144: 561-568. PMID: 24619174, DOI: 10.1007/s10549-014-2904-z.Peer-Reviewed Original ResearchConceptsDNA copy numberBiological processesIndividual molecular eventsCopy numberGene expressionMolecular eventsMulticellular organismal processGene Ontology databaseGO biological processesSignal transduction pathwaysOrganismal processesGO termsMolecular dataTransduction pathwaysSiRNA screenComplex genomic abnormalitiesIndividual cancersOntology databaseFunctional roleDriver eventsCell growthSequence abnormalitiesBreast cancer cell linesCancer cell linesGenomic abnormalities
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
2012
A network-based, integrative study to identify core biological pathways that drive breast cancer clinical subtypes
Dutta B, Pusztai L, Qi Y, André F, Lazar V, Bianchini G, Ueno N, Agarwal R, Wang B, Shiang CY, Hortobagyi GN, Mills GB, Symmans WF, Balázsi G. A network-based, integrative study to identify core biological pathways that drive breast cancer clinical subtypes. British Journal Of Cancer 2012, 106: 1107-1116. PMID: 22343619, PMCID: PMC3304402, DOI: 10.1038/bjc.2011.584.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCell Line, TumorComputer SimulationDNA Copy Number VariationsEpithelial-Mesenchymal TransitionFemaleGene ExpressionGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesGene Regulatory NetworksGenes, NeoplasmHumansModels, BiologicalProtein Interaction MapsReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRNA InterferenceConceptsGenome-scale dataCore biological pathwaysTriple receptor-negative breast cancerProtein-protein interactionsCell line data setsGene knockdown experimentsGene copy number dataCopy number dataCopy number variation dataNumber variation dataMember genesGene networksTranscriptional disturbancesKnockdown experimentsBiological discoveryGene expressionFunctional specificityBiological pathwaysDifferential expressionIntegrative studyFunctional relevanceVariation dataLine data setsCell linesGenes