2015
Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets
Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, Van Allen EM, Lawrence MS, Horowitz PM, Cibulskis K, Ligon KL, Tabernero J, Seoane J, Martinez-Saez E, Curry WT, Dunn IF, Paek SH, Park SH, McKenna A, Chevalier A, Rosenberg M, Barker FG, Gill CM, Van Hummelen P, Thorner AR, Johnson BE, Hoang MP, Choueiri TK, Signoretti S, Sougnez C, Rabin MS, Lin NU, Winer EP, Stemmer-Rachamimov A, Meyerson M, Garraway L, Gabriel S, Lander ES, Beroukhim R, Batchelor TT, Baselga J, Louis DN, Getz G, Hahn WC. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discovery 2015, 5: 1164-1177. PMID: 26410082, PMCID: PMC4916970, DOI: 10.1158/2159-8290.cd-15-0369.Peer-Reviewed Original ResearchConceptsBrain metastasesPrimary tumorPrimary biopsiesRegional lymph node metastasisLymph node metastasisPI3K/Akt/mTORRegional lymph nodesPotential therapeutic targetPrimary tumor biopsiesPrimary tumor samplesAkt/mTORDistinct genetic alterationsWhole-exome sequencingExtracranial metastasesLymph nodesNode metastasisDismal prognosisActionable alterationsMetastasis sitesInformative alterationsIndividualized therapyTherapeutic targetMetastasisPrimary siteEGFR inhibitors
2013
Integration of Cell Line and Clinical Trial Genome-Wide Analyses Supports a Polygenic Architecture of Paclitaxel-Induced Sensory Peripheral Neuropathy
Wheeler HE, Gamazon ER, Wing C, Njiaju UO, Njoku C, Baldwin RM, Owzar K, Jiang C, Watson D, Shterev I, Kubo M, Zembutsu H, Winer EP, Hudis CA, Shulman LN, Nakamura Y, Ratain MJ, Kroetz DL, B F, Cox NJ, Dolan ME. Integration of Cell Line and Clinical Trial Genome-Wide Analyses Supports a Polygenic Architecture of Paclitaxel-Induced Sensory Peripheral Neuropathy. Clinical Cancer Research 2013, 19: 491-499. PMID: 23204130, PMCID: PMC3549006, DOI: 10.1158/1078-0432.ccr-12-2618.Peer-Reviewed Original ResearchConceptsExpression quantitative trait lociSingle nucleotide polymorphismsPolygenic architectureGenome-wide association study resultsLymphoblastoid cell line (LCL) modelGenome-wide analysisSignificant enrichmentQuantitative trait lociRegulatory factor X (RFX) familyAssociation study resultsRelevant genetic variantsGWAS resultsTrait lociAllelic directionCell line modelsRelated traitsHapMap projectEnrichment resultsPaclitaxel-induced cytotoxicityCellular modelReduced neurite outgrowthGenetic variantsRFX2Neurite outgrowthCell lines
2012
A Genome-Wide Association Study Identifies Novel Loci for Paclitaxel-Induced Sensory Peripheral Neuropathy in CALGB 40101
Baldwin RM, Owzar K, Zembutsu H, Chhibber A, Kubo M, Jiang C, Watson D, Eclov RJ, Mefford J, McLeod HL, Friedman PN, Hudis CA, Winer EP, Jorgenson EM, Witte JS, Shulman LN, Nakamura Y, Ratain MJ, Kroetz DL. A Genome-Wide Association Study Identifies Novel Loci for Paclitaxel-Induced Sensory Peripheral Neuropathy in CALGB 40101. Clinical Cancer Research 2012, 18: 5099-5109. PMID: 22843789, PMCID: PMC3445665, DOI: 10.1158/1078-0432.ccr-12-1590.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, PhytogenicBreast NeoplasmsFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansIncidenceMicrofilament ProteinsMiddle AgedPaclitaxelPeripheral Nervous System DiseasesPolymorphism, Single NucleotideReceptor, EphA5Sensory Receptor CellsConceptsSensory peripheral neuropathyWide association studyPeripheral neuropathyCALGB 40101Genome-wide association study identifies novel lociAssociation studiesPrimary breast cancerIdentification of patientsNovel genetic markersGenetic risk factorsAfrican American subjectsSingle nucleotide polymorphismsAdditional EuropeanNovel lociPaclitaxel armAdditional genesGenetic variationPaclitaxel therapyClinical managementRisk factorsBreast cancerDiscovery cohortPharmacogenetic analysisNeuropathyGenetic markers