2023
Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
de Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, PMCID: PMC10957226, DOI: 10.1016/j.ccell.2023.07.005.Peer-Reviewed Original ResearchConceptsMammalian SWI/SNF chromatinSWI/SNF chromatinMSWI/SNF complexesGenome-wide localizationGene regulatory signaturesNon-genetic mechanismsEpithelial cell differentiationEGFR-mutant cellsChromatin accessibilitySNF complexCellular programsRegulatory signaturesTKI-resistant lung cancerGene targetsKinase inhibitor resistanceCell differentiationMesenchymal transitionTKI resistancePharmacologic disruptionTyrosine kinase inhibitor resistanceCell proliferationChromatinInhibitor resistanceEGFR-mutant lungKinase inhibitors
2021
Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma
Fisk JN, Mahal AR, Dornburg A, Gaffney SG, Aneja S, Contessa JN, Rimm D, Yu JB, Townsend JP. Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma. Cancer Letters 2021, 526: 346-351. PMID: 34780851, PMCID: PMC8702484, DOI: 10.1016/j.canlet.2021.11.011.Peer-Reviewed Original ResearchConceptsMutational processesSingle ancestral lineageAncestral lineageProgression of cancerMetastatic lineagesPhylogenetic analysisGenetic resistanceEvolutionary processesExogenous mutational processesCancer evolutionConsolidative therapyMutational signature analysisEGFR-positive non-small cell lung cancerNon-small cell lung cancerKey eventsLineagesCell populationsTherapeutic resistanceLocal consolidative therapyClinical time courseCell lung cancerDisease etiologyTherapeutic decision makingCisplatin therapyLung cancer
2019
Performance Comparison of Different Analytic Methods in Proficiency Testing for Mutations in the BRAF, EGFR, and KRAS Genes: A Study of the College of American Pathologists Molecular Oncology Committee
Moncur JT, Bartley AN, Bridge JA, Kamel-Reid S, Lazar AJ, Lindeman NI, Long TA, Merker JD, Rai AJ, Rimm DL, Rothberg PG, Vasalos P, Kim AS. Performance Comparison of Different Analytic Methods in Proficiency Testing for Mutations in the BRAF, EGFR, and KRAS Genes: A Study of the College of American Pathologists Molecular Oncology Committee. Archives Of Pathology & Laboratory Medicine 2019, 143: 1203-1211. PMID: 30969158, DOI: 10.5858/arpa.2018-0396-cp.Peer-Reviewed Original Research
2018
Immune Marker Profiling and Programmed Death Ligand 1 Expression Across NSCLC Mutations
Toki MI, Mani N, Smithy JW, Liu Y, Altan M, Wasserman B, Tuktamyshov R, Schalper K, Syrigos KN, Rimm DL. Immune Marker Profiling and Programmed Death Ligand 1 Expression Across NSCLC Mutations. Journal Of Thoracic Oncology 2018, 13: 1884-1896. PMID: 30267840, PMCID: PMC6251746, DOI: 10.1016/j.jtho.2018.09.012.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPD-L1TIL activationHigh PD-L1 levelsDeath ligand 1 (PD-L1) expressionActivation statusKRAS wild-type tumorsKRAS mutantEGFR mutantsHigh PD-L1Multiplexed quantitative immunofluorescenceUnique immune profilePD-L1 levelsLigand 1 expressionDeath-1/EGFR-mutant tumorsImmunotherapy response ratesKRAS mutant tumorsWild-type tumorsHigher CD4NSCLC patientsImmune profileClinical efficacyKRAS WTLymphocyte populationsComparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing
Kim AS, Bartley AN, Bridge JA, Kamel-Reid S, Lazar AJ, Lindeman NI, Long TA, Merker JD, Rai AJ, Rimm DL, Rothberg PG, Vasalos P, Moncur JT. Comparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing. JAMA Oncology 2018, 4: 838-841. PMID: 29242895, PMCID: PMC6145687, DOI: 10.1001/jamaoncol.2017.4021.Peer-Reviewed Original ResearchConceptsLaboratory-developed testsPT responseCompanion diagnosticsClinical laboratory testingKRAS testingOncology CommitteeMAIN OUTCOMEUS FoodDrug AdministrationPractice characteristicsDiagnostic testingTumor contentProficiency testingVariant-specific differencesEGFRBRAFClinical diagnostic testingMajority of laboratoriesKRASAssaysLaboratory testingPerformance of laboratoriesKit manufacturersResponseParticipants
2017
Worldwide Frequency of Commonly Detected EGFR Mutations
Graham RP, Treece AL, Lindeman NI, Vasalos P, Shan M, Jennings LJ, Rimm DL. Worldwide Frequency of Commonly Detected EGFR Mutations. Archives Of Pathology & Laboratory Medicine 2017, 142: 163-167. PMID: 29106293, DOI: 10.5858/arpa.2016-0579-cp.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungErbB ReceptorsGenes, erbB-1HumansLaboratory Proficiency TestingMutationConceptsEGFR mutationsResistance mutationsEpidermal growth factor receptor (EGFR) mutationsProficiency testing programEGFR inhibitor therapyAmerican Pathologists Proficiency Testing ProgramCommon resistance mutationsT790M mutationClinical laboratoriesCalendar year 2013Mutation frequencyInhibitor therapyCommon mutation sitesLung cancerPulmonary adenocarcinomaL858R mutationReceptor mutationsFrequency of mutationsActivating mutationsEGFR inhibitorsM mutationAsian femalesExon 18Exon 20Ethnic differencesErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC
Alvarado D, Ligon GF, Lillquist JS, Seibel SB, Wallweber G, Neumeister VM, Rimm DL, McMahon G, LaVallee TM. ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC. PLOS ONE 2017, 12: e0181356. PMID: 28723928, PMCID: PMC5517012, DOI: 10.1371/journal.pone.0181356.Peer-Reviewed Original ResearchConceptsNeuregulin-1NRG1 expressionErbB3 activationNeck squamous cell carcinomaSquamous cell carcinomaEnhanced anti-tumor activitySubset of HNSCCUnmet medical needHNSCC cell linesHNSCC patient samplesAnti-tumor activityGrowth factor αLigand neuregulin-1Cell carcinomaEGFR/ErbB familyHNSCC modelsCetuximab treatmentErbB receptor inhibitionReceptor inhibitionReceptor levelsRespective signaling pathwaysSolid tumorsTumor typesHNSCCPotential biomarkersProof of the quantitative potential of immunofluorescence by mass spectrometry
Toki MI, Cecchi F, Hembrough T, Syrigos KN, Rimm DL. Proof of the quantitative potential of immunofluorescence by mass spectrometry. Laboratory Investigation 2017, 97: 329-334. PMID: 28092364, PMCID: PMC5334147, DOI: 10.1038/labinvest.2016.148.Peer-Reviewed Original Research
2016
EGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma
Toki MI, Carvajal-Hausdorf DE, Altan M, McLaughlin J, Henick B, Schalper KA, Syrigos KN, Rimm DL. EGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma. Journal Of Thoracic Oncology 2016, 11: 1901-1911. PMID: 27449805, PMCID: PMC5075503, DOI: 10.1016/j.jtho.2016.06.025.Peer-Reviewed Original ResearchConceptsEGFR pathway activationSeries of patientsLung adenocarcinomaMutation statusEGFR expressionPathway activationProximity ligation assayKRAS wild-type tumorsEGFR-mutant patientsKRAS-mutant casesCohort of patientsWild-type tumorsInteraction of EGFREGFR expression levelsEGFR protein expressionMAPK/ERK pathwayGrowth factor receptorActive EGFRPrognostic factorsDifferent mutation statusPatient groupPrognostic valueLonger survivalEGFR mutationsPrognostic markerOncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells
Forloni M, Gupta R, Nagarajan A, Sun LS, Dong Y, Pirazzoli V, Toki M, Wurtz A, Melnick MA, Kobayashi S, Homer RJ, Rimm DL, Gettinger SJ, Politi K, Dogra SK, Wajapeyee N. Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells. Cell Reports 2016, 16: 457-471. PMID: 27346347, PMCID: PMC4945411, DOI: 10.1016/j.celrep.2016.05.087.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAntineoplastic AgentsBrain NeoplasmsCCAAT-Enhancer-Binding ProteinsCell Line, TumorCpG IslandsDNA MethylationDrug Screening Assays, AntitumorErbB ReceptorsGene Expression Regulation, NeoplasticGene SilencingGlioblastomaHumansLung NeoplasmsMAP Kinase Signaling SystemMixed Function OxygenasesMutationOncogenesProtein Kinase InhibitorsProto-Oncogene ProteinsTranscription, GeneticTumor Suppressor ProteinsUp-RegulationConceptsOncogenic epidermal growth factor receptorMethylation-mediated transcriptional silencingEpidermal growth factor receptorTumor suppressorTranscriptional silencingActive DNA demethylationCancer cellsFamily member 1TET1 knockdownDNA demethylaseDNA demethylationTranscription factorsGrowth factor receptorEctopic expressionCytoplasmic localizationGlioblastoma tumor growthLung cancer cellsTET1 expressionFunctional roleSuppressorFactor receptorMember 1TET1SilencingLung cancer samples
2014
EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial
Cheng H, Ballman K, Vassilakopoulou M, Dueck AC, Reinholz MM, Tenner K, Gralow J, Hudis C, Davidson NE, Fountzilas G, McCullough AE, Chen B, Psyrri A, Rimm DL, Perez EA. EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial. British Journal Of Cancer 2014, 111: 1065-1071. PMID: 25117817, PMCID: PMC4453859, DOI: 10.1038/bjc.2014.442.Peer-Reviewed Original ResearchConceptsNorth Central Cancer Treatment GroupMetastatic breast cancer cohortEpidermal growth factor receptorBreast cancer cohortHigh EGFR expressionEGFR expressionConcurrent trastuzumabGrowth factor receptorCancer cohortEGFR antibodyNCCTG N9831 trialsAnti-HER2 therapyCancer Treatment GroupDisease-free survivalFactor receptorN9831 trialsSequential trastuzumabAdditive therapyArm AClinical outcomesTreatment optionsWorse outcomesArm CTissue microarrayTreatment groups
2013
Molecular profile of head and neck squamous cell carcinomas bearing p16 high phenotype
Rampias T, Pectasides E, Prasad M, Sasaki C, Gouveris P, Dimou A, Kountourakis P, Perisanidis C, Burtness B, Zaramboukas T, Rimm D, Fountzilas G, Psyrri A. Molecular profile of head and neck squamous cell carcinomas bearing p16 high phenotype. Annals Of Oncology 2013, 24: 2124-2131. PMID: 23406730, DOI: 10.1093/annonc/mdt013.Peer-Reviewed Original ResearchMeSH KeywordsBeta CateninBiomarkers, TumorCarcinoma, Squamous CellCell Line, TumorCyclin-Dependent Kinase Inhibitor p16ErbB ReceptorsFemaleHead and Neck NeoplasmsHumansMaleNeoplasm ProteinsOncogene Proteins, ViralOropharyngeal NeoplasmsPapillomavirus E7 ProteinsPapillomavirus InfectionsPhosphorylationPTEN PhosphohydrolaseRepressor ProteinsRNA InterferenceRNA, Small InterferingSquamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53Wnt Signaling PathwayConceptsE6/E7Β-cateninHNSCC cellsTissue microarrayE6/E7 repressionEpidermal growth factor receptor (EGFR) pathwayNeck squamous cell cancerE6/E7 genesOropharyngeal cancer cellsNeck squamous cell carcinomaShort hairpin RNAGrowth factor receptor pathwayHPV16 E6/E7Squamous cell cancerSquamous cell carcinomaExpression of biomarkersExpression differencesPTEN upregulationAberrant EGFRE7 repressionHairpin RNAMedian OSOverall survivalPhosphorylated EGFRCell cancer
2011
Standardization of Epidermal Growth Factor Receptor (EGFR) Measurement by Quantitative Immunofluorescence and Impact on Antibody-Based Mutation Detection in Non–Small Cell Lung Cancer
Dimou A, Agarwal S, Anagnostou V, Viray H, Christensen S, Rothberg B, Zolota V, Syrigos K, Rimm DL. Standardization of Epidermal Growth Factor Receptor (EGFR) Measurement by Quantitative Immunofluorescence and Impact on Antibody-Based Mutation Detection in Non–Small Cell Lung Cancer. American Journal Of Pathology 2011, 179: 580-589. PMID: 21722621, PMCID: PMC3157192, DOI: 10.1016/j.ajpath.2011.04.031.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerPrognostic valueMutation-specific antibodiesLung cancerQuantitative immunofluorescenceEpidermal growth factor receptor (EGFR) protein expressionIndependent NSCLC cohortsPopulation-based cohortEGFR mutation rateReceptor protein expressionTotal proteinFalse-positive casesPrediction of responseWestern blot analysisNSCLC cohortRetrospective cohortReceptor measurementsYale cohortEGFR expressionCohortEGFRAQUA technologyProtein expressionAntibodiesGefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study
Osborne CK, Neven P, Dirix LY, Mackey JR, Robert J, Underhill C, Schiff R, Gutierrez C, Migliaccio I, Anagnostou VK, Rimm DL, Magill P, Sellers M. Gefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study. Clinical Cancer Research 2011, 17: 1147-1159. PMID: 21220480, PMCID: PMC3074404, DOI: 10.1158/1078-0432.ccr-10-1869.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug-Related Side Effects and Adverse ReactionsErbB ReceptorsFemaleGefitinibHumansMiddle AgedNeoplasms, Hormone-DependentPlacebosQuinazolinesReceptor, ErbB-2Receptors, EstrogenSignal TransductionTamoxifenTreatment OutcomeConceptsAdjuvant aromatase inhibitorsMetastatic breast cancerBreast cancerHormone receptor-positive metastatic breast cancerPositive metastatic breast cancerRandomized phase II studyRandomized phase II trialClinical benefit ratePhase II studyPhase II trialProgression-free survivalStratum 1Epidermal growth factor receptor inhibitor gefitinibFurther investigationAdjuvant tamoxifenImproved PFSPFS HRAI therapyII studyII trialMetastatic diseaseAppropriate patientsPredictive biomarkersPrimary tumorTamoxifen resistance
2010
The ERα coactivator, HER4/4ICD, regulates progesterone receptor expression in normal and malignant breast epithelium
Rokicki J, Das PM, Giltnane JM, Wansbury O, Rimm DL, Howard BA, Jones FE. The ERα coactivator, HER4/4ICD, regulates progesterone receptor expression in normal and malignant breast epithelium. Molecular Cancer 2010, 9: 150. PMID: 20550710, PMCID: PMC2894764, DOI: 10.1186/1476-4598-9-150.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorErbB ReceptorsEstrogen Receptor alphaFemaleGene ExpressionGene Expression RegulationHumansMammary Glands, AnimalMammary Glands, HumanMiceMice, TransgenicPregnancyReceptor, ErbB-4Receptors, ProgesteroneReverse Transcriptase Polymerase Chain ReactionSignal TransductionConceptsPgR expressionExpression of PgRBreast cancerERα coactivatorMammary glandHER4 intracellular domainProgesterone receptor expressionPositive breast carcinomaMalignant breast epitheliumPrimary breast tumorsMCF-7 variantEstrogen receptor coactivatorBreast tumor cell linesCell linesBreast tumor cellsTamoxifen responseMouse mammary glandProgesterone receptorReceptor expressionBreast carcinomaMCF-7 breast tumor cell linePatient responseBreast carcinogenesisEstrogen stimulationBreast epitheliumAnalytic Variability in Immunohistochemistry Biomarker Studies
Anagnostou VK, Welsh AW, Giltnane JM, Siddiqui S, Liceaga C, Gustavson M, Syrigos KN, Reiter JL, Rimm DL. Analytic Variability in Immunohistochemistry Biomarker Studies. Cancer Epidemiology Biomarkers & Prevention 2010, 19: 982-991. PMID: 20332259, PMCID: PMC3891912, DOI: 10.1158/1055-9965.epi-10-0097.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 3Cancer patientsEstrogen receptorWestern blottingBiomarker studiesEpidermal growth factor receptor 1Breast cancer patientsLung cancer patientsEpidermal growth factor receptor 3Growth factor receptor 1Factor receptor 1Growth factor receptor 3Clone 1D5Worse prognosisHigher eGFRPrognostic classificationER antibodyCancer-related biomarkersCutoff pointBT474 cellsSurvival analysisEGFR antibodyReceptor 1Receptor 3Quantitative immunofluorescence
2009
Quantitative multiplexed analysis of ErbB family coexpression for primary breast cancer prognosis in a large retrospective cohort
Giltnane JM, Moeder CB, Camp RL, Rimm DL. Quantitative multiplexed analysis of ErbB family coexpression for primary breast cancer prognosis in a large retrospective cohort. Cancer 2009, 115: 2400-2409. PMID: 19330842, PMCID: PMC2756449, DOI: 10.1002/cncr.24277.Peer-Reviewed Original ResearchAssociation of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells
Agarwal S, Zerillo C, Kolmakova J, Christensen JG, Harris LN, Rimm DL, DiGiovanna MP, Stern DF. Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells. British Journal Of Cancer 2009, 100: 941-949. PMID: 19240716, PMCID: PMC2661782, DOI: 10.1038/sj.bjc.6604937.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorEGFR/HER2 inhibitorsNSCLC cell linesDual EGFR/HER2 inhibitorsGrowth factor receptorMET inhibitorsHER2 inhibitorsUse of EGFREGFR tyrosine kinase inhibitorsCell lung cancer cellsFactor receptorMajority of patientsTreatment of NSCLCCell lung carcinomaTyrosine kinase inhibitorsPotential therapeutic advantagesSubset of tumorsLung cancer cellsCell linesCurrent clinical useReceptor TKTumor cell growthHepatocyte growth factor receptorMaximal growth inhibitionImportant molecular target
2008
Correlates and Determinants of Nuclear Epidermal Growth Factor Receptor Content in an Oropharyngeal Cancer Tissue Microarray
Psyrri A, Egleston B, Pectasides E, Weinberger P, Yu Z, Kowalski D, Sasaki C, Haffty B, Rimm D, Burtness B. Correlates and Determinants of Nuclear Epidermal Growth Factor Receptor Content in an Oropharyngeal Cancer Tissue Microarray. Cancer Epidemiology Biomarkers & Prevention 2008, 17: 1486-1492. PMID: 18559565, DOI: 10.1158/1055-9965.epi-07-2684.Peer-Reviewed Original Research
2007
Hormonal Markers in Breast Cancer: Coexpression, Relationship with Pathologic Characteristics, and Risk Factor Associations in a Population-Based Study
Yang XR, Pfeiffer RM, Garcia-Closas M, Rimm DL, Lissowska J, Brinton LA, Peplonska B, Hewitt SM, Cartun RW, Mandich D, Sasano H, Evans DB, Sutter TR, Sherman ME. Hormonal Markers in Breast Cancer: Coexpression, Relationship with Pathologic Characteristics, and Risk Factor Associations in a Population-Based Study. Cancer Research 2007, 67: 10608-10617. PMID: 17968031, DOI: 10.1158/0008-5472.can-07-2142.Peer-Reviewed Original ResearchConceptsCurrent body mass indexBody mass indexPremenopausal womenPathologic characteristicsMass indexHormonal markersMolecular subtypesHigher current body mass indexPopulation-based case-control studyProliferation factorsEpidemiologic risk factorsRisk factor associationsHigh tumor gradeCase-control studyInvasive breast carcinomaBreast cancer tissuesER betaRisk factorsTumor gradeBreast carcinomaCoexpression patternsBreast cancerHigher scoresEarly menarcheCancer tissues