2021
Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer
Kocakavuk E, Anderson K, Varn F, Johnson K, Amin S, Sulman E, Lolkema M, Barthel F, Verhaak R. Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer. Nature Genetics 2021, 53: 1088-1096. PMID: 34045764, PMCID: PMC8483261, DOI: 10.1038/s41588-021-00874-3.Peer-Reviewed Original ResearchConceptsWorse clinical outcomesNon-irradiated tumorsClinical outcomesRecurrent cancerPatient survivalPoor outcomeMetastatic tumorsRecurrent gliomaRadiation therapyRadiation-induced DNA damageDNA damageGlioma Longitudinal Analysis ConsortiumMutational signature analysisCancer treatmentDeletion burdenRadiotherapyMedical FoundationAPOBEC mutagenesisSignificant increaseTumorsCancerDNA damage repairDeletion signatureMutational spectrumSmall deletions
2020
Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers
Kim H, Nguyen N, Turner K, Wu S, Gujar A, Luebeck J, Liu J, Deshpande V, Rajkumar U, Namburi S, Amin S, Yi E, Menghi F, Schulte J, Henssen A, Chang H, Beck C, Mischel P, Bafna V, Verhaak R. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nature Genetics 2020, 52: 891-897. PMID: 32807987, PMCID: PMC7484012, DOI: 10.1038/s41588-020-0678-2.Peer-Reviewed Original ResearchConceptsOncogene amplificationPoor outcomeCancer typesEcDNA amplificationShorter survivalCancer patientsMost cancer typesExtrachromosomal DNA amplificationsClinical impactMultiple cancersPatientsNormal tissuesCancerTranscript fusionsEnhanced chromatin accessibilityIntratumoral genetic heterogeneityOncogene transcriptionChromosomal amplificationOutcomesGenetic heterogeneityHigh levelsDNA amplificationTissue typesBloodKMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer
Alam H, Tang M, Maitituoheti M, Dhar S, Kumar M, Han C, Ambati C, Amin S, Gu B, Chen T, Lin Y, Chen J, Muller F, Putluri N, Flores E, DeMayo F, Baseler L, Rai K, Lee M. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer Cell 2020, 37: 599-617.e7. PMID: 32243837, PMCID: PMC7178078, DOI: 10.1016/j.ccell.2020.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAnimalsAntimetabolitesApoptosisBiomarkers, TumorCell ProliferationDeoxyglucoseDNA-Binding ProteinsEnhancer Elements, GeneticGene Expression Regulation, NeoplasticGlycolysisHistone-Lysine N-MethyltransferaseHistonesHumansLung NeoplasmsMiceMice, KnockoutMice, NudeMutationMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsPeriod Circadian ProteinsPrognosisTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsLung cancerLung-specific lossHuman lung cancer cellsExpression of Per2Lung cancer cellsHistone methyltransferase KMT2DLung tumor suppressorTumor suppressive roleMultiple glycolytic genesLung tumorigenesisEpigenetic modifiersPharmacological inhibitionTherapeutic vulnerabilitiesGlycolytic inhibitorCancerCancer cellsKMT2DFunction mutationsTumor suppressorPer2GlycolysisGlycolytic genesMutationsMice
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