2020
Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure
Akdemir K, Le V, Kim J, Killcoyne S, King D, Lin Y, Tian Y, Inoue A, Amin S, Robinson F, Nimmakayalu M, Herrera R, Lynn E, Chan K, Seth S, Klimczak L, Gerstung M, Gordenin D, O’Brien J, Li L, Deribe Y, Verhaak R, Campbell P, Fitzgerald R, Morrison A, Dixon J, Andrew Futreal P. Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure. Nature Genetics 2020, 52: 1178-1188. PMID: 33020667, PMCID: PMC8350746, DOI: 10.1038/s41588-020-0708-0.Peer-Reviewed Original ResearchConceptsCancer genomesMutational processesGenome organizationThree-dimensional genome organizationThree-dimensional chromatin structureSomatic mutationsSpatial genome organizationMutation rate variationDifferent human cancer typesDifferent mutational processesWhole-genome datasetsActive mutational processesSpecific mutational processesChromatin structureHuman cancer typesMutation distributionInactive domainsDevelopment of cancerDriver genesGenomeMutational loadActive domainHuman cancersMutationsNovel therapeutic strategiesEnhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma
Maitituoheti M, Keung E, Tang M, Yan L, Alam H, Han G, Singh A, Raman A, Terranova C, Sarkar S, Orouji E, Amin S, Sharma S, Williams M, Samant N, Dhamdhere M, Zheng N, Shah T, Shah A, Axelrad J, Anvar N, Lin Y, Jiang S, Chang E, Ingram D, Wang W, Lazar A, Lee M, Muller F, Wang L, Ying H, Rai K. Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma. Cell Reports 2020, 33: 108293. PMID: 33086062, PMCID: PMC7649750, DOI: 10.1016/j.celrep.2020.108293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell Line, TumorDNA-Binding ProteinsFemaleGenes, Tumor SuppressorGlucoseGlycolysisHistone MethyltransferasesHistone-Lysine N-MethyltransferaseHumansInsulinIntercellular Signaling Peptides and ProteinsMaleMelanomaMiceMice, Inbred C57BLMice, NudeMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsReceptor, IGF Type 1Regulatory Sequences, Nucleic AcidSignal TransductionXenograft Model Antitumor AssaysConceptsKMT2D-deficient cellsInsulin growth factorEnhancer reprogrammingIGF1R-AktMelanocyte-specific deletionMutant melanomaMouse modelTumor typesTherapeutic interventionsPharmacological inhibitionPathway inhibitorPotent tumor suppressorIGF signalingGrowth factorMelanomaPooled RNAi screensSomatic point mutationsTumor suppressorKey metabolic pathwaysFrequent lossGlycolysisGlycolysis enzymesTumorigenesisGlycolysis pathwayMetabolic pathways
2019
p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors
Carugo A, Minelli R, Sapio L, Soeung M, Carbone F, Robinson F, Tepper J, Chen Z, Lovisa S, Svelto M, Amin S, Srinivasan S, Del Poggetto E, Loponte S, Puca F, Dey P, Malouf G, Su X, Li L, Lopez-Terrada D, Rakheja D, Lazar A, Netto G, Rao P, Sgambato A, Maitra A, Tripathi D, Walker C, Karam J, Heffernan T, Viale A, Roberts C, Msaouel P, Tannir N, Draetta G, Genovese G. p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors. Cancer Cell 2019, 35: 204-220.e9. PMID: 30753823, PMCID: PMC7876656, DOI: 10.1016/j.ccell.2019.01.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAutophagyCell Line, TumorCyclin-Dependent Kinase Inhibitor p16Endoplasmic Reticulum StressFemaleGene Expression Regulation, NeoplasticHumansMaleMice, 129 StrainMice, Inbred C57BLMice, KnockoutProteasome InhibitorsProteostasisProto-Oncogene Proteins c-mycRhabdoid TumorSignal TransductionSMARCB1 ProteinTumor Cells, CulturedTumor Suppressor Protein p53Unfolded Protein ResponseConceptsMalignant rhabdoid tumorRhabdoid tumorUnfolded protein responseClinical pathological featuresAggressive pediatric malignancyCombination of agentsPediatric malignanciesMouse modelP53 axisMosaic mouse modelChromatin remodeling genesER stress responseTumorsHuman oncogenesisBiallelic inactivationMalignancyProtein responseDramatic activationHuman diseasesMaster regulatorExquisite sensitivityAutophagic machineryAgentsDiseaseStress response
2018
An in vivo screen identifies PYGO2 as a driver for metastatic prostate cancer
Lu X, Pan X, Wu C, Zhao D, Feng S, Zang Y, Lee R, Khadka S, Amin S, Jin E, Shang X, Deng P, Luo Y, Morgenlander W, Weinrich J, Lu X, Jiang S, Chang Q, Navone N, Troncoso P, DePinho R, Wang Y. An in vivo screen identifies PYGO2 as a driver for metastatic prostate cancer. Cancer Research 2018, 78: canres.3564.2017. PMID: 29769196, PMCID: PMC6381393, DOI: 10.1158/0008-5472.can-17-3564.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCarcinogenesisCell Line, TumorDisease ProgressionGene Expression Regulation, NeoplasticHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsLymph NodesMaleMiceMice, NudeNeoplasm GradingOncogenesPC-3 CellsProstatic NeoplasmsTranscriptional ActivationUp-RegulationWnt Signaling PathwayConceptsProstate cancer progressionDepth functional analysisCancer progressionWnt/β-catenin signalingCancer cell invasionΒ-catenin signalingFunctional genomicsProstate cancerTranscriptional activationCopy number aberrationsTranscriptomic datasetsFinger 2New oncogenePygo2's functionFunctional driversFunctional analysisLymph nodesImpairs tumor progressionChromosomal instabilityPutative oncogeneCell invasionNumber aberrationsPositive hitsAmplification/overexpressionOncogene
2017
Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer
Genovese G, Carugo A, Tepper J, Robinson F, Li L, Svelto M, Nezi L, Corti D, Minelli R, Pettazzoni P, Gutschner T, Wu C, Seth S, Akdemir K, Leo E, Amin S, Molin M, Ying H, Kwong L, Colla S, Takahashi K, Ghosh P, Giuliani V, Muller F, Dey P, Jiang S, Garvey J, Liu C, Zhang J, Heffernan T, Toniatti C, Fleming J, Goggins M, Wood L, Sgambato A, Agaimy A, Maitra A, Roberts C, Wang H, Viale A, DePinho R, Draetta G, Chin L. Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer. Nature 2017, 542: 362-366. PMID: 28178232, PMCID: PMC7609022, DOI: 10.1038/nature21064.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Pancreatic DuctalDeoxycytidineEndoplasmic Reticulum StressFemaleGemcitabineGenes, mycGenes, rasHumansMaleMAP Kinase Kinase 4MAP Kinase Signaling SystemMesodermMiceMosaicismOncogene Protein p55(v-myc)Pancreatic NeoplasmsProteolysisProto-Oncogene Proteins p21(ras)SMARCB1 ProteinTranscriptome
2015
The Molecular Taxonomy of Primary Prostate Cancer
Network T, Abeshouse A, Ahn J, Akbani R, Ally A, Amin S, Andry C, Annala M, Aprikian A, Armenia J, Arora A, Auman J, Balasundaram M, Balu S, Barbieri C, Bauer T, Benz C, Bergeron A, Beroukhim R, Berrios M, Bivol A, Bodenheimer T, Boice L, Bootwalla M, dos Reis R, Boutros P, Bowen J, Bowlby R, Boyd J, Bradley R, Breggia A, Brimo F, Bristow C, Brooks D, Broom B, Bryce A, Bubley G, Burks E, Butterfield Y, Button M, Canes D, Carlotti C, Carlsen R, Carmel M, Carroll P, Carter S, Cartun R, Carver B, Chan J, Chang M, Chen Y, Cherniack A, Chevalier S, Chin L, Cho J, Chu A, Chuah E, Chudamani S, Cibulskis K, Ciriello G, Clarke A, Cooperberg M, Corcoran N, Costello A, Cowan J, Crain D, Curley E, David K, Demchok J, Demichelis F, Dhalla N, Dhir R, Doueik A, Drake B, Dvinge H, Dyakova N, Felau I, Ferguson M, Frazer S, Freedland S, Fu Y, Gabriel S, Gao J, Gardner J, Gastier-Foster J, Gehlenborg N, Gerken M, Gerstein M, Getz G, Godwin A, Gopalan A, Graefen M, Graim K, Gribbin T, Guin R, Gupta M, Hadjipanayis A, Haider S, Hamel L, Hayes D, Heiman D, Hess J, Hoadley K, Holbrook A, Holt R, Holway A, Hovens C, Hoyle A, Huang M, Hutter C, Ittmann M, Iype L, Jefferys S, Jones C, Jones S, Juhl H, Kahles A, Kane C, Kasaian K, Kerger M, Khurana E, Kim J, Klein R, Kucherlapati R, Lacombe L, Ladanyi M, Lai P, Laird P, Lander E, Latour M, Lawrence M, Lau K, LeBien T, Lee D, Lee S, Lehmann K, Leraas K, Leshchiner I, Leung R, Libertino J, Lichtenberg T, Lin P, Linehan W, Ling S, Lippman S, Liu J, Liu W, Lochovsky L, Loda M, Logothetis C, Lolla L, Longacre T, Lu Y, Luo J, Ma Y, Mahadeshwar H, Mallery D, Mariamidze A, Marra M, Mayo M, McCall S, McKercher G, Meng S, Mes-Masson A, Merino M, Meyerson M, Mieczkowski P, Mills G, Shaw K, Minner S, Moinzadeh A, Moore R, Morris S, Morrison C, Mose L, Mungall A, Murray B, Myers J, Naresh R, Nelson J, Nelson M, Nelson P, Newton Y, Noble M, Noushmehr H, Nykter M, Pantazi A, Parfenov M, Park P, Parker J, Paulauskis J, Penny R, Perou C, Piché A, Pihl T, Pinto P, Prandi D, Protopopov A, Ramirez N, Rao A, Rathmell W, Rätsch G, Ren X, Reuter V, Reynolds S, Rhie S, Rieger-Christ K, Roach J, Robertson A, Robinson B, Rubin M, Saad F, Sadeghi S, Saksena G, Saller C, Salner A, Sanchez-Vega F, Sander C, Sandusky G, Sauter G, Sboner A, Scardino P, Scarlata E, Schein J, Schlomm T, Schmidt L, Schultz N, Schumacher S, Seidman J, Neder L, Seth S, Sharp A, Shelton C, Shelton T, Shen H, Shen R, Sherman M, Sheth M, Shi Y, Shih J, Shmulevich I, Simko J, Simon R, Simons J, Sipahimalani P, Skelly T, Sofia H, Soloway M, Song X, Sorcini A, Sougnez C, Stepa S, Stewart C, Stewart J, Stuart J, Sullivan T, Sun C, Sun H, Tam A, Tan D, Tang J, Tarnuzzer R, Tarvin K, Taylor B, Teebagy P, Tenggara I, Têtu B, Tewari A, Thiessen N, Thompson T, Thorne L, Tirapelli D, Tomlins S, Trevisan F, Troncoso P, True L, Tsourlakis M, Tyekucheva S, Van Allen E, Van Den Berg D, Veluvolu U, Verhaak R, Vocke C, Voet D, Wan Y, Wang Q, Wang W, Wang Z, Weinhold N, Weinstein J, Weisenberger D, Wilkerson M, Wise L, Witte J, Wu C, Wu J, Wu Y, Xu A, Yadav S, Yang L, Yang L, Yau C, Ye H, Yena P, Zeng T, Zenklusen J, Zhang H, Zhang J, Zhang J, Zhang W, Zhong Y, Zhu K, Zmuda E. The Molecular Taxonomy of Primary Prostate Cancer. Cell 2015, 163: 1011-1025. PMID: 26544944, PMCID: PMC4695400, DOI: 10.1016/j.cell.2015.10.025.Peer-Reviewed Original ResearchConceptsPrimary prostate cancerProstate cancerVariable clinical courseAndrogen receptor activityPrimary prostate carcinomasSubtype-specific mannerSubstantial heterogeneityMolecular taxonomyCancer Genome AtlasClinical courseSpecific gene fusionsProstate carcinomaMutant tumorsReceptor activityComprehensive molecular analysisMolecular abnormalitiesCancerDNA repair genesMethylator phenotypeActionable lesionsGenome AtlasPI3KRepair genesEpigenetic profilesTumors
2014
MicroRNA expression patterns in medullary and extramedullary plasmacytoma
Lin J, Mahindra A, Santo L, Amin S, Sohani A, Raje N. MicroRNA expression patterns in medullary and extramedullary plasmacytoma. Blood Cancer Journal 2014, 4: e223-e223. PMID: 24972152, PMCID: PMC4080212, DOI: 10.1038/bcj.2014.41.Peer-Reviewed Original Research
2011
Significant Biological Role of Sp1 Transactivation in Multiple Myeloma
Fulciniti M, Amin S, Nanjappa P, Rodig S, Prabhala R, Li C, Minvielle S, Tai Y, Tassone P, Avet-Loiseau H, Hideshima T, Anderson K, Munshi N. Significant Biological Role of Sp1 Transactivation in Multiple Myeloma. Clinical Cancer Research 2011, 17: 6500-6509. PMID: 21856768, PMCID: PMC4318245, DOI: 10.1158/1078-0432.ccr-11-1036.Peer-Reviewed Original ResearchConceptsBone marrow stromal cellsSp1 activitySp1 knockdownTranscription factor specificity protein 1Caspase-9-dependent apoptosisCritical cell cycleSp1 DNA bindingSp1-responsive promotersSpecificity protein 1Cell growthFirefly luciferase reporter geneImportant transcription factorImportant regulatory roleLuciferase reporter geneSignificant biological roleApoptosis-related genesSp1 transactivationShort hairpin RNASp1 DNACellular processesTranscription factorsPromoter elementsMarrow stromal cellsReporter geneMM cells
2010
Elevated IL-17 produced by T h 17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma
Prabhala R, Pelluru D, Fulciniti M, Prabhala H, Nanjappa P, Song W, Pai C, Amin S, Tai Y, Richardson P, Ghobrial I, Treon S, Daley J, Anderson K, Kutok J, Munshi N. Elevated IL-17 produced by T h 17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood 2010, 115: 5385-5392. PMID: 20395418, PMCID: PMC2902136, DOI: 10.1182/blood-2009-10-246660.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHealthy donor peripheral blood mononuclear cellsDonor peripheral blood mononuclear cellsIL-17Multiple myelomaBM mononuclear cellsMyeloma cell growthBone marrowBone marrow stromal cellsIL-22Mononuclear cellsHealthy donorsImmune functionT helper 17 (Th17) cellsElevated IL-17Observed immune dysfunctionSerum IL-17IL-23 productionBlood mononuclear cellsAnti-MM activityIL-17 receptorHuman multiple myelomaMurine xenograft modelImportant therapeutic targetMM pathobiology