2021
Using Machine Learning Algorithms to Predict Immunotherapy Response in Patients with Advanced Melanoma
Johannet P, Coudray N, Donnelly DM, Jour G, Illa-Bochaca I, Xia Y, Johnson DB, Wheless L, Patrinely JR, Nomikou S, Rimm DL, Pavlick AC, Weber JS, Zhong J, Tsirigos A, Osman I. Using Machine Learning Algorithms to Predict Immunotherapy Response in Patients with Advanced Melanoma. Clinical Cancer Research 2021, 27: 131-140. PMID: 33208341, PMCID: PMC7785656, DOI: 10.1158/1078-0432.ccr-20-2415.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedDisease ProgressionDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedImmune Checkpoint InhibitorsMachine LearningMaleMelanomaMiddle AgedNeoplasm StagingPrognosisProgression-Free SurvivalProspective StudiesRisk AssessmentROC CurveSkinSkin NeoplasmsConceptsProgression-free survivalImmune checkpoint inhibitorsLower riskClinicodemographic characteristicsAdvanced melanomaClinical dataWorse progression-free survivalICI treatment outcomesKaplan-Meier curvesBiomarkers of responseStandard of careCheckpoint inhibitorsICI responseImmunotherapy responseValidation cohortTraining cohortDisease progressionProspective validationTreatment outcomesHigh riskClinical practicePatientsROC curveProgressionRisk
2019
Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death
Kulkarni PM, Robinson EJ, Pradhan J, Gartrell-Corrado RD, Rohr BR, Trager MH, Geskin LJ, Kluger HM, Wong PF, Acs B, Rizk EM, Yang C, Mondal M, Moore MR, Osman I, Phelps R, Horst BA, Chen ZS, Ferringer T, Rimm DL, Wang J, Saenger YM. Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death. Clinical Cancer Research 2019, 26: 1126-1134. PMID: 31636101, PMCID: PMC8142811, DOI: 10.1158/1078-0432.ccr-19-1495.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlgorithmsArea Under CurveBiopsyDeep LearningDisease ProgressionFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedMaleMelanomaMiddle AgedNeoplasm Recurrence, LocalNeural Networks, ComputerRetrospective StudiesRisk FactorsStaining and LabelingSurvival RateYoung AdultConceptsDeep neural network architectureNeural network architectureDeep learningNetwork architectureComputational modelImage sequencesDigital imagesVote aggregationDisease-specific survivalDSS predictionPractical advancesComputational methodsIHC-based methodsImagesGeisinger Health SystemNovel methodGHS patientsArchitectureLearningKaplan-Meier analysisPrimary melanoma tumorsEarly-stage melanomaClinical trial designModelAdjuvant immunotherapy
2018
Immunological differences between primary and metastatic breast cancer
Szekely B, Bossuyt V, Li X, Wali VB, Patwardhan GA, Frederick C, Silber A, Park T, Harigopal M, Pelekanou V, Zhang M, Yan Q, Rimm DL, Bianchini G, Hatzis C, Pusztai L. Immunological differences between primary and metastatic breast cancer. Annals Of Oncology 2018, 29: 2232-2239. PMID: 30203045, DOI: 10.1093/annonc/mdy399.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyBreast NeoplasmsDisease ProgressionDrug Resistance, NeoplasmFemaleGene Expression RegulationHumansImmunologic SurveillanceLymphocyte CountLymphocytes, Tumor-InfiltratingMiddle AgedMutation RateTumor EscapeTumor MicroenvironmentYoung AdultConceptsMetastatic breast cancerBreast cancerTherapeutic targetToll-like receptor pathway genesImmuno-oncology therapeutic targetsBreast cancer evolvesImmune proteasome expressionPD-L1 positivityCorresponding primary tumorsPotential therapeutic targetMHC class IImmune-related genesMetastatic cancer samplesLigand/receptor pairLymphocyte countT helperT-regsPD-L1Immune microenvironmentCytotoxic TPrimary tumorMastoid cellsDisease progressionTherapeutic combinationsMacrophage markers
2016
RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clinical Cancer Research 2016, 22: 1499-1509. PMID: 26515496, PMCID: PMC4794351, DOI: 10.1158/1078-0432.ccr-15-1125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenBiomarkersCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleGene Expression ProfilingHumansImmunomodulationImmunophenotypingLymphocytes, Tumor-InfiltratingMiceMitogen-Activated Protein KinasesMortalityPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsRas ProteinsSignal TransductionTranscriptomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesImmune checkpoint inhibitorsResidual diseaseNeoadjuvant chemotherapyBreast cancerPD-L1Checkpoint inhibitorsMHC expressionMouse modelPD-1/PD-L1 immune checkpoint inhibitorsPD-L1 immune checkpoint inhibitorsPresence of TILsPD-1/PD-L1Low tumor-infiltrating lymphocytesPD-L1/PDAntitumor immune responseRAS/MAPK activationCell-surface MHC expressionMAPK activationImproved survivalImproved prognosisPredictive biomarkersClinical trialsImmune response
2013
High Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer
Liu M, Mor G, Cheng H, Xiang X, Hui P, Rutherford T, Yin G, Rimm DL, Holmberg J, Alvero A, Silasi DA. High Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer. Reproductive Sciences 2013, 20: 605-615. PMID: 23171677, PMCID: PMC3635069, DOI: 10.1177/1933719112461183.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnalysis of VarianceBiomarkers, TumorCarcinoma, Ovarian EpithelialDisease ProgressionDisease-Free SurvivalDrug Resistance, NeoplasmFemaleHumansHyaluronan ReceptorsKaplan-Meier EstimateKeratin-19Middle AgedMultivariate AnalysisNeoplasm Recurrence, LocalNeoplasm StagingNeoplasms, Glandular and EpithelialNeoplastic Stem CellsOvarian NeoplasmsProportional Hazards ModelsRetrospective StudiesRisk FactorsTime FactorsTreatment OutcomeConceptsPutative ovarian cancer stem cellsOvarian cancer stem cellsProgression-free intervalCancer stem cellsRecurrent epithelial ovarian cancerShorter disease-free intervalShorter progression-free intervalDisease-free intervalResidual tumor volumeEpithelial ovarian cancerLog-rank testEpithelial ovarian cancer cellsIndependent significant predictorsAdvanced stage EOCOvarian cancer cellsStem cellsMean followObstetrics stageUnivariable analysisClinicopathologic featuresMultivariable analysisRetrospective studyPrognostic valueOvarian cancerTumor volume
2012
Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes
Peck AR, Witkiewicz AK, Liu C, Klimowicz AC, Stringer GA, Pequignot E, Freydin B, Yang N, Ertel A, Tran TH, Girondo MA, Rosenberg AL, Hooke JA, Kovatich AJ, Shriver CD, Rimm DL, Magliocco AM, Hyslop T, Rui H. Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes. Breast Cancer Research 2012, 14: r130. PMID: 23036105, PMCID: PMC4053108, DOI: 10.1186/bcr3328.Peer-Reviewed Original ResearchConceptsPoor prognosisBreast cancerClinical outcomesIndependent markerNode-negative breast cancer patientsNode-negative breast cancerLower tumor levelsPrimary breast cancerUnfavorable clinical outcomeBreast cancer patientsClinical outcome dataProtein levelsRandomized clinical trialsPredictors of responseNew independent markerBreast cancer progressionTherapy-naïveFourfold riskCancer patientsTherapy failureTumor levelsArchival cohortUnfavorable outcomeClinical trialsStat5a/b
2011
Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure
Peck AR, Witkiewicz AK, Liu C, Stringer GA, Klimowicz AC, Pequignot E, Freydin B, Tran TH, Yang N, Rosenberg AL, Hooke JA, Kovatich AJ, Nevalainen MT, Shriver CD, Hyslop T, Sauter G, Rimm DL, Magliocco AM, Rui H. Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure. Journal Of Clinical Oncology 2011, 29: 2448-2458. PMID: 21576635, PMCID: PMC3675698, DOI: 10.1200/jco.2010.30.3552.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, Intraductal, NoninfiltratingCohort StudiesDisease ProgressionDisease-Free SurvivalDrug Resistance, NeoplasmEstrogen Receptor ModulatorsFemaleHumansLymphatic MetastasisMiddle AgedNeoplasm ProteinsNuclear ProteinsPhosphorylationPhosphotyrosinePrognosisProtein Processing, Post-TranslationalSTAT5 Transcription FactorSurvival AnalysisTreatment FailureTumor Suppressor ProteinsYoung AdultConceptsNode-negative breast cancerCancer-specific survivalIndependent prognostic markerBreast cancerWhole tissue sectionsTherapy failurePrognostic markerTissue microarrayPathologist scoringMultivariate analysis patientsSystemic adjuvant therapyAdjuvant hormone therapyMarker of prognosisPoor clinical outcomeUseful predictive markerPredictors of responseNormal breast epitheliumTissue sectionsCohort IVAdjuvant therapyHormone therapyAnalysis patientsClinical outcomesDuctal carcinomaProspective studyIn vitro studies of dasatinib, its targets and predictors of sensitivity
Jilaveanu LB, Zito CR, Aziz SA, Chakraborty A, Davies MA, Camp RL, Rimm DL, Dudek A, Sznol M, Kluger HM. In vitro studies of dasatinib, its targets and predictors of sensitivity. Pigment Cell & Melanoma Research 2011, 24: 386-389. PMID: 21320292, PMCID: PMC4431976, DOI: 10.1111/j.1755-148x.2011.00835.x.Peer-Reviewed Original ResearchDifferential expression of arrestins is a predictor of breast cancer progression and survival
Michal AM, Peck AR, Tran TH, Liu C, Rimm DL, Rui H, Benovic JL. Differential expression of arrestins is a predictor of breast cancer progression and survival. Breast Cancer Research And Treatment 2011, 130: 791-807. PMID: 21318602, PMCID: PMC3156829, DOI: 10.1007/s10549-011-1374-9.Peer-Reviewed Original ResearchConceptsBreast cancer progressionBreast cancerCancer progressionArrestin2 expressionLuminal linesMyoepithelial cellsNormal human breast tissueMetastatic breast cancerLymph node metastasisPoor clinical outcomeIndependent prognostic markerPrimary breast tumorsBreast cancer cell linesG protein-coupled receptorsArrestin2 levelsPositive lymphCancer cell linesHazard ratioHuman breast tissueProtein-coupled receptorsNode metastasisClinical outcomesDuctal carcinomaTumor sizeNuclear grade
2010
PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer
VanHouten J, Sullivan C, Bazinet C, Ryoo T, Camp R, Rimm DL, Chung G, Wysolmerski J. PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 11405-11410. PMID: 20534448, PMCID: PMC2895115, DOI: 10.1073/pnas.0911186107.Peer-Reviewed Original ResearchConceptsPMCA2 expressionBreast cancerT47D breast cancer cellsIntracellular calcium levelsBreast cancer progressionBreast cancer cellsEpithelial cell apoptosisPoor outcomeIntracellular calciumCalcium levelsMammary gland involutionCancer progressionCell apoptosisCancer cellsMammary involutionApoptosisGland involutionCancerMammary epithelial cell apoptosisOutcomesPMCA2Triggers apoptosisApical surfaceExpressionOverexpression
2009
Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays
Mehnert JM, McCarthy MM, Jilaveanu L, Flaherty KT, Aziz S, Camp RL, Rimm DL, Kluger HM. Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays. Human Pathology 2009, 41: 375-384. PMID: 20004943, PMCID: PMC2824079, DOI: 10.1016/j.humpath.2009.08.016.Peer-Reviewed Original ResearchBlotting, WesternCell LineDisease ProgressionHumansImage Processing, Computer-AssistedImmunohistochemistryMelanomaNevusProportional Hazards ModelsRegression AnalysisSeverity of Illness IndexSkin NeoplasmsStatistics, NonparametricTissue Array AnalysisVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas
Jilaveanu LB, Zito CR, Aziz SA, Conrad PJ, Schmitz JC, Sznol M, Camp RL, Rimm DL, Kluger HM. C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas. Clinical Cancer Research 2009, 15: 5704-5713. PMID: 19737955, PMCID: PMC2763114, DOI: 10.1158/1078-0432.ccr-09-0198.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBenzenesulfonatesCell Line, TumorCell ProliferationCell SurvivalCohort StudiesDisease ProgressionFemaleGene SilencingHumansIndolesMaleMelanomaMiddle AgedNevusNiacinamidePhenolsPhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-rafPyridinesRNA, Small InterferingSensitivity and SpecificitySkin NeoplasmsSorafenibYoung AdultConceptsExtracellular signal-regulated kinaseC-RafC-Raf expressionSubset of melanomasPhospho-c-RafSignal-regulated kinaseCell linesProtein kinase inhibitionMitogen-activated protein kinase inhibitionDecreased viabilityDecreased Bcl-2 expressionProtein kinaseCell signalingBcl-2 inhibitionRaf kinaseB-RafMelanoma cell linesPhospho-MEKSpecific siRNAsSitu protein expressionGW5074Major isoformsKinasePhospho-ERKBcl-2 expressionThe Semaphorin 7A Receptor Plexin C1 Is Lost During Melanoma Metastasis
Lazova R, Rothberg BE, Rimm D, Scott G. The Semaphorin 7A Receptor Plexin C1 Is Lost During Melanoma Metastasis. American Journal Of Dermatopathology 2009, 31: 177-181. PMID: 19318806, DOI: 10.1097/dad.0b013e318196672d.Peer-Reviewed Original ResearchConceptsTumor suppressor proteinHuman melanocytesPlexin C1Suppressor proteinPlexin C1 receptorsMelanocyte stem cellsCytoskeletal reorganizationNeuronal pathfindingDownstream targetsKinase IIProgression of melanomaBlood vessel growthCell survivalCell adhesionCell migrationFunctional studiesNormal melanocytesCell growthCognate receptorsStem cellsCritical mediatorMelanocytesSemaphorin 7AVessel growthSemaphorins
2008
Genomic analysis of estrogen cascade reveals histone variant H2A.Z associated with breast cancer progression
Hua S, Kallen CB, Dhar R, Baquero MT, Mason CE, Russell BA, Shah PK, Liu J, Khramtsov A, Tretiakova MS, Krausz TN, Olopade OI, Rimm DL, White KP. Genomic analysis of estrogen cascade reveals histone variant H2A.Z associated with breast cancer progression. Molecular Systems Biology 2008, 4: msb200825. PMID: 18414489, PMCID: PMC2394496, DOI: 10.1038/msb.2008.25.Peer-Reviewed Original ResearchConceptsHistone variant H2A.ZVariant H2A.ZBreast cancer progressionTranscription factor-binding sitesTranscriptional regulatory cascadeCancer progressionGenome tiling arraysWhole-genome mappingFactor-binding sitesRegulatory cascadeTiling arraysChromatin immunoprecipitationGenome mappingGenomic analysisH2A.Z levelsRNA interferenceGene targetsGene expressionEpigenetic factorsMicroarray screeningH2A.ZCell proliferationLymph node metastasisBreast cancer survivalHigh expression
2007
HSP90 as a marker of progression in melanoma
McCarthy MM, Pick E, Kluger Y, Gould-Rothberg BE, Lazova R, Camp RL, Rimm DL, Kluger HM. HSP90 as a marker of progression in melanoma. Annals Of Oncology 2007, 19: 590-594. PMID: 18037622, DOI: 10.1093/annonc/mdm545.Peer-Reviewed Original Research
2005
Altered Localization of p120 Catenin During Epithelial to Mesenchymal Transition of Colon Carcinoma Is Prognostic for Aggressive Disease
Bellovin DI, Bates RC, Muzikansky A, Rimm DL, Mercurio AM. Altered Localization of p120 Catenin During Epithelial to Mesenchymal Transition of Colon Carcinoma Is Prognostic for Aggressive Disease. Cancer Research 2005, 65: 10938-10945. PMID: 16322241, DOI: 10.1158/0008-5472.can-05-1947.Peer-Reviewed Original ResearchConceptsSurvival timeMesenchymal transitionLymph node metastasisColorectal cancer progressionPoor patient outcomesE-cadherinLate-stage tumorsPatient survival timePost-EMT cellsP120ctn expressionAltered localizationLymph nodesNode metastasisAggressive diseaseTumor stagePrimary tumorTumor necrosisColorectal carcinomaPatient outcomesColon carcinoma cellsE-cadherin lossCytoplasmic stainingColon carcinomaCancer progressionCarcinoma cellsIntegrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma
Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 2005, 436: 117-122. PMID: 16001072, DOI: 10.1038/nature03664.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCell LineageCell SurvivalChromosomes, Human, Pair 3Disease ProgressionDNA-Binding ProteinsGene AmplificationGene DosageGene Expression Regulation, NeoplasticGenomicsHumansIn Situ Hybridization, FluorescenceMelanomaMicrophthalmia-Associated Transcription FactorOncogenesPolymerase Chain ReactionPolymorphism, Single NucleotideTranscription FactorsConceptsMITF gene expressionDNA amplification eventsIntegrative genomic analysisLineage-survival oncogenePossible drug targetsGenomics effortsGenomic analysisGenetic dataGene expressionMelanoma formationAmplification eventsMelanoma genesDrug targetsCancer cell linesGenetic alterationsCell linesMITFMelanoma cellsHuman melanomaMalignant melanomaGenesMelanomaOncogeneExpressionCellsUpstaging based solely on positive peritoneal washing does not affect outcome in endometrial cancer
Fadare O, Mariappan MR, Hileeto D, Wang, Mcalpine JN, Rimm DL. Upstaging based solely on positive peritoneal washing does not affect outcome in endometrial cancer. Modern Pathology 2005, 18: 673-680. PMID: 15578078, DOI: 10.1038/modpathol.3800342.Peer-Reviewed Original ResearchConceptsEndometrial carcinomaControl groupEndometrial cancerPeritoneal washingsPrognostic significanceStage IAge-matched control groupPositive peritoneal washingsSame histologic subtypeEndometrial carcinoma patientsPeritoneal washing cytologyProgression of diseaseExtra-uterine tumoursSingle-site studyExtrauterine diseasePositive washingsAbnormal cytologyAdjuvant therapySurgical stagingPositive cytologyCarcinoma patientsHistologic subtypeWashing cytologyHistologic evidenceIntraperitoneal disease
2003
Detection of chromosomal instability in paired breast surgery and ductal lavage specimens by interphase fluorescence in situ hybridization.
King BL, Tsai SC, Gryga ME, D'Aquila TG, Seelig SA, Morrison LE, Jacobson KK, Legator MS, Ward DC, Rimm DL, Phillips RF. Detection of chromosomal instability in paired breast surgery and ductal lavage specimens by interphase fluorescence in situ hybridization. Clinical Cancer Research 2003, 9: 1509-16. PMID: 12684427.Peer-Reviewed Original ResearchConceptsDuctal lavageMalignant casesBenign casesBreast lesionsBreast cellsInvasive breast cancerInterphase fluorescenceBreast cancer progressionAbnormal cytologyLavage cellsSitu hybridizationBreast surgeryBreast cancerEarly neoplasiaConventional cytologyLavageGenetic abnormalitiesCancer progressionNew modalityNumeric changesSitu hybridization analysisSurgeryLesionsCytologyAbnormalities
2001
Novel inactivating mutations of transforming growth factor‐β type I receptor gene in head‐and‐neck cancer metastases
Chen T, Yan W, Wells R, Rimm D, McNiff J, Leffell D, Reiss M. Novel inactivating mutations of transforming growth factor‐β type I receptor gene in head‐and‐neck cancer metastases. International Journal Of Cancer 2001, 93: 653-661. PMID: 11477574, DOI: 10.1002/ijc.1381.Peer-Reviewed Original ResearchMeSH KeywordsActivin Receptors, Type IAmino Acid SequenceDisease ProgressionEndoplasmic ReticulumFemaleHead and Neck NeoplasmsHumansMaleMolecular Sequence DataMutationNeoplasms, Glandular and EpithelialNeoplasms, Unknown PrimaryProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IReceptors, Transforming Growth Factor betaSequence Homology, Amino AcidSignal TransductionTransforming Growth Factor betaConceptsT beta RNeck cancer metastasisTGF-beta signalingCancer metastasisBeta RTGF betaBeta signalingLate-stage diseaseHuman epithelial neoplasmsCorresponding primary tumorsBreast cancer metastasisFine needle aspiratesTGF-beta type I receptorNovel inactivating mutationsBeta type I receptorType I receptorStage diseaseCarcinoma cell linesPrimary tumorCell cycle arrestEpithelial neoplasmsCodon 387MetastasisI receptorHuman tumors