2018
Increased epigenetic age in normal breast tissue from luminal breast cancer patients
Hofstatter EW, Horvath S, Dalela D, Gupta P, Chagpar AB, Wali VB, Bossuyt V, Storniolo AM, Hatzis C, Patwardhan G, Von Wahlde MK, Butler M, Epstein L, Stavris K, Sturrock T, Au A, Kwei S, Pusztai L. Increased epigenetic age in normal breast tissue from luminal breast cancer patients. Clinical Epigenetics 2018, 10: 112. PMID: 30157950, PMCID: PMC6114717, DOI: 10.1186/s13148-018-0534-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsBreastBreast NeoplasmsCase-Control StudiesCpG IslandsDNA MethylationEpigenesis, GeneticFemaleHigh-Throughput Nucleotide SequencingHumansMiddle AgedSequence Analysis, DNATissue BanksConceptsNormal breast tissueBreast cancer patientsBreast cancerCancer patientsEpigenetic age accelerationBreast tissueAge accelerationLuminal breast cancer patientsNormal adjacent breast tissueNormal breast tissue samplesIncident breast cancerTissue samplesNon-tumor sitesBreast cancer riskImportant risk factorAdjacent breast tissueKomen Tissue BankChronological ageBreast cancer statusMalignant breast tissueNormal tissue samplesAge-related changesBreast tissue samplesBreast surgeryUnaffected women
2017
Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer
Chung JH, Pavlick D, Hartmaier R, Schrock AB, Young L, Forcier B, Ye P, Levin MK, Goldberg M, Burris H, Gay LM, Hoffman AD, Stephens PJ, Frampton GM, Lipson DM, Nguyen DM, Ganesan S, Park BH, Vahdat LT, Leyland-Jones B, Mughal TI, Pusztai L, O’Shaughnessy J, Miller VA, Ross JS, Ali SM. Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer. Annals Of Oncology 2017, 28: 2866-2873. PMID: 28945887, PMCID: PMC5834148, DOI: 10.1093/annonc/mdx490.Peer-Reviewed Original ResearchConceptsEstrogen receptor-positive metastatic breast cancerMetastatic breast cancerBreast cancerGenomic profilingGenomic alterationsEstrogen receptor-positive breast cancerMetastatic breast cancer managementReceptor-positive breast cancerTumor DNACo-occurring genomic alterationsMetastatic tissue biopsiesTissue samplesRoutine clinical careBreast cancer managementCourse of diseasePeripheral blood samplesMetastatic tumor tissueMetastatic diseaseFemale patientsInvasive alternativeCtDNA fractionCancer managementClinical careBlood samplesPatients
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 abnormalitiesMutation based treatment recommendations from next generation sequencing data: a comparison of web tools
Patel JM, Knopf J, Reiner E, Bossuyt V, Epstein L, DiGiovanna M, Chung G, Silber A, Sanft T, Hofstatter E, Mougalian S, Abu-Khalaf M, Platt J, Shi W, Gershkovich P, Hatzis C, Pusztai L. Mutation based treatment recommendations from next generation sequencing data: a comparison of web tools. Oncotarget 2016, 7: 22064-22076. PMID: 26980737, PMCID: PMC5008344, DOI: 10.18632/oncotarget.8017.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsDrug Therapy, Computer-AssistedFemaleHigh-Throughput Nucleotide SequencingHumansInternetMolecular Targeted TherapyPrecision MedicineSoftwareConceptsWeb toolArtificial intelligence toolsApplicable software toolsReal-time statusDifferent web toolsIntelligence toolsSoftware toolsRecommendation toolGeneration sequencing dataNext-generation sequencing dataData acquisitionInteraction databasesGenomic dataRecommendation sourcesCancer genome dataProfiling resultsToolDrug-gene interaction databaseMore sourcesGenome dataAlgorithmPlatformPersonalized cancer therapy
2015
Standardization efforts enabling next-generation sequencing and microarray based biomarkers for precision medicine
Zheng Y, Qing T, Song Y, Zhu J, Yu Y, Shi W, Pusztai L, Shi L. Standardization efforts enabling next-generation sequencing and microarray based biomarkers for precision medicine. Biomarkers In Medicine 2015, 9: 1265-1272. PMID: 26502353, DOI: 10.2217/bmm.15.99.Peer-Reviewed Original ResearchBiomarkersHigh-Throughput Nucleotide SequencingHumansOligonucleotide Array Sequence AnalysisPrecision MedicineReference StandardsTranslational Research, BiomedicalA 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 regressionCharacterization of DNA variants in the human kinome in breast cancer
Agarwal D, Qi Y, Jiang T, Liu X, Shi W, Wali VB, Turk B, Ross JS, Fraser Symmans W, Pusztai L, Hatzis C. Characterization of DNA variants in the human kinome in breast cancer. Scientific Reports 2015, 5: 14736. PMID: 26420498, PMCID: PMC4588561, DOI: 10.1038/srep14736.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBreast NeoplasmsFemaleGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseGenetic VariationHigh-Throughput Nucleotide SequencingHumansMiddle AgedMutationNeoplasm GradingNeoplasm MetastasisNeoplasm StagingPhosphotransferasesPolymorphism, Single NucleotideReproducibility of ResultsTranscriptomeConceptsBreast cancerHuman kinomeKinase geneGreater mutational loadNucleic acid variationPrimary cancer samplesPrimary breast cancerHistologic grade 1Major functional impactSOLiD sequencing platformIndividual breast cancersNon-synonymous variantsFine-needle biopsyGrade 3 casesCancer-related genesNucleotide variationsDNA variantsSequencing platformsMetastatic lesionsMutational loadAcid variationsCancer biologyGenesNeedle biopsyAdditional cancersReproducibility of Variant Calls in Replicate Next Generation Sequencing Experiments
Qi Y, Liu X, Liu CG, Wang B, Hess KR, Symmans WF, Shi W, Pusztai L. Reproducibility of Variant Calls in Replicate Next Generation Sequencing Experiments. PLOS ONE 2015, 10: e0119230. PMID: 26136146, PMCID: PMC4489803, DOI: 10.1371/journal.pone.0119230.Peer-Reviewed Original ResearchMeSH KeywordsAllelesArtifactsBreast NeoplasmsDNAFemaleGene FrequencyGenome, HumanHigh-Throughput Nucleotide SequencingHumansPolymorphism, Single NucleotideProtein KinasesReproducibility of ResultsSequence Analysis, DNAConceptsSingle nucleotide variantsEuropean Genome-phenome ArchiveProtein kinase geneMillions of nucleotidesSame genomic DNANext-generation sequencing experimentsVariant callsGenomic locationNext-generation sequencingSequence dataSNV callsKinase geneGenomic DNANucleotide substitutionsSequencing experimentsHigh stringencyVariant allele frequencyNucleotide variantsTrue biological changeNucleotide alterationsGeneration sequencingAllele countsSequencing errorsBreast cancer samplesAllele frequencies
2014
A Targeted Next‐Generation Sequencing Assay Detects a High Frequency of Therapeutically Targetable Alterations in Primary and Metastatic Breast Cancers: Implications for Clinical Practice
Vasan N, Yelensky R, Wang K, Moulder S, Dzimitrowicz H, Avritscher R, Wang B, Wu Y, Cronin MT, Palmer G, Symmans WF, Miller VA, Stephens P, Pusztai L. A Targeted Next‐Generation Sequencing Assay Detects a High Frequency of Therapeutically Targetable Alterations in Primary and Metastatic Breast Cancers: Implications for Clinical Practice. The Oncologist 2014, 19: 453-458. PMID: 24710307, PMCID: PMC4012963, DOI: 10.1634/theoncologist.2013-0377.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBase SequenceBreast NeoplasmsFemaleGenomicsHigh-Throughput Nucleotide SequencingHumansMiddle AgedMolecular Targeted TherapyMutationPrecision MedicineSequence Analysis, DNAConceptsBreast cancerGenomic alterationsV-akt murine thymoma viral oncogene homolog 1Stage IV cancerMetastatic breast cancerActionable genomic alterationsPotential treatment optionOncogene homolog 1Primary tumor biopsiesCancer-related genesClinical Laboratory Improvement AmendmentsDependent kinasesMedian sequencing depthGene fusionsSequencing depthBase substitutionsHER2 mutationsHomolog 1Actionable alterationsTargetable alterationsTreatment optionsClinical trialsHER2 amplificationMetastatic cancerTumor biopsiesEmergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer
Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, Ferrer-Lozano J, Perez-Fidalgo JA, Cristofanilli M, Gómez H, Arteaga CL, Giltnane J, Balko JM, Cronin MT, Jarosz M, Sun J, Hawryluk M, Lipson D, Otto G, Ross JS, Dvir A, Soussan-Gutman L, Wolf I, Rubinek T, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Brown M, Miller VA. Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer. Clinical Cancer Research 2014, 20: 1757-1767. PMID: 24398047, PMCID: PMC3998833, DOI: 10.1158/1078-0432.ccr-13-2332.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsEstrogen Receptor alphaFemaleHigh-Throughput Nucleotide SequencingHumansMCF-7 CellsMutationNeoplasm StagingNeoplasms, Hormone-DependentConceptsEstrogen receptor α mutationBreast cancerAdvanced estrogen receptor-positive breast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerHormone-dependent breast cancerPrimary breast cancerSubgroup of patientsER-negative tumorsLine of treatmentCodon 537ER- diseaseEndocrine treatmentTreatment-naïveESR1 mutationsMetastatic diseaseCell line modelsEndocrine resistanceMetastatic tumorsReceptor constitutive activityEstrogen receptorMetastatic samplesTumor specimensCancer-related genesNatural history
2010
Molecular profiling contributes more than routine histology and immonohistochemistry to breast cancer diagnostics
Shiang C, Pusztai L. Molecular profiling contributes more than routine histology and immonohistochemistry to breast cancer diagnostics. Breast Cancer Research 2010, 12: s6. PMID: 21172090, PMCID: PMC3005726, DOI: 10.1186/bcr2735.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsDNA FingerprintingFemaleGene Expression ProfilingGenomicsHigh-Throughput Nucleotide SequencingHumansImmunohistochemistryMolecular Diagnostic TechniquesReceptors, Estrogen