Featured Publications
Pervasive lesion segregation shapes cancer genome evolution
Aitken S, Anderson C, Connor F, Pich O, Sundaram V, Feig C, Rayner T, Lukk M, Aitken S, Luft J, Kentepozidou E, Arnedo-Pac C, Beentjes S, Davies S, Drews R, Ewing A, Kaiser V, Khamseh A, López-Arribillaga E, Redmond A, Santoyo-Lopez J, Sentís I, Talmane L, Yates A, Semple C, López-Bigas N, Flicek P, Odom D, Taylor M. Pervasive lesion segregation shapes cancer genome evolution. Nature 2020, 583: 265-270. PMID: 32581361, PMCID: PMC7116693, DOI: 10.1038/s41586-020-2435-1.Peer-Reviewed Original ResearchConceptsChromosome-scale phasingDNA lesionsAcquisition of oncogenic mutationsAlternative allelesGenetic diversityMultiple cell generationsCancer genomesLesion segregationDNA replicationMutagenic DNA lesionsDaughter cellsBase pairsCell divisionCell cycleExogenous mutagensHuman cellsOncogenic selectionOncogenic mutationsMouse liver tumorsDNACell generationDNA base pairsMutationsCellsGenomeCTCF maintains regulatory homeostasis of cancer pathways
Aitken S, Ibarra-Soria X, Kentepozidou E, Flicek P, Feig C, Marioni J, Odom D. CTCF maintains regulatory homeostasis of cancer pathways. Genome Biology 2018, 19: 106. PMID: 30086769, PMCID: PMC6081938, DOI: 10.1186/s13059-018-1484-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCCCTC-Binding FactorCell LineChromatinDNA, NeoplasmEnhancer Elements, GeneticFemaleFibroblastsGene Expression Regulation, NeoplasticGenomeHemizygoteHomeostasisHumansLiver Neoplasms, ExperimentalMiceMice, Inbred C57BLMice, TransgenicProtein BindingSignal TransductionUterine NeoplasmsConceptsTranscriptional regulationIntra-TAD interactionsSteady-state gene expressionCancer-related pathwaysMammalian genomesCTCF occupancyGenome functionChromatin loopsEvolutionary conservationChromatin structureGenomic dysregulationRegulatory domainHemizygous cellsEpigenomic profilingCTCFCTCF expressionMammalian cellsExpressed genesAffinity binding eventsTranscriptional alterationsGene expressionMouse lineagesCancer pathwaysMouse model systemHuman cancers
2020
IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis
Siersbæk R, Scabia V, Nagarajan S, Chernukhin I, Papachristou E, Broome R, Johnston S, Joosten S, Green A, Kumar S, Jones J, Omarjee S, Alvarez-Fernandez R, Glont S, Aitken S, Kishore K, Cheeseman D, Rakha E, D'Santos C, Zwart W, Russell A, Brisken C, Carroll J. IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis. Cancer Cell 2020, 38: 412-423.e9. PMID: 32679107, PMCID: PMC7116707, DOI: 10.1016/j.ccell.2020.06.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, HormonalBreast NeoplasmsEnhancer Elements, GeneticEstrogen Receptor alphaFemaleFulvestrantGene Expression ProfilingGene Expression Regulation, NeoplasticHumansInterleukin-6Kaplan-Meier EstimateMCF-7 CellsMice, Inbred NODMice, KnockoutMice, SCIDNeoplasm MetastasisSignal TransductionSTAT3 Transcription FactorXenograft Model Antitumor AssaysConceptsEstrogen receptor aInhibition of STAT3 activationOncogenic pathwaysBreast cancer invasionSTAT3 activationTranscriptional programsDownstream effector STAT3STAT3IL6/STAT3 signalingIndependent of ERCancer invasionER enhancementER-targeted therapiesBreast cancerCytokine interleukin-6Interleukin-6PathwayIL6/STAT3Receptor A