Featured Publications
Titration of RAS alters senescent state and influences tumour initiation
Chan A, Zhu H, Narita M, Cassidy L, Young A, Bermejo-Rodriguez C, Janowska A, Chen H, Gough S, Oshimori N, Zender L, Aitken S, Hoare M, Narita M. Titration of RAS alters senescent state and influences tumour initiation. Nature 2024, 633: 678-685. PMID: 39112713, PMCID: PMC11410659, DOI: 10.1038/s41586-024-07797-z.Peer-Reviewed Original ResearchConceptsTumor typesOncogenic RAS-induced senescenceInfluence tumor initiationProgenitor-like featuresTumor-initiating phenotypeSingle-cell RNA sequencing analysisModel in vivoHCC subclassesModel in vitroHepatocellular carcinomaTumor suppressor mechanismEarly tumorigenesisTumor initiationEarly-onsetProgenitor featuresInduce tumorsSuppressor mechanismTumorLate-onsetRNA sequencing analysisOncogenic stressRas-induced senescenceIn vivoMolecular signaturesOncogene dosageConvergent somatic mutations in metabolism genes in chronic liver disease
Ng S, Rouhani F, Brunner S, Brzozowska N, Aitken S, Yang M, Abascal F, Moore L, Nikitopoulou E, Chappell L, Leongamornlert D, Ivovic A, Robinson P, Butler T, Sanders M, Williams N, Coorens T, Teague J, Raine K, Butler A, Hooks Y, Wilson B, Birtchnell N, Naylor H, Davies S, Stratton M, Martincorena I, Rahbari R, Frezza C, Hoare M, Campbell P. Convergent somatic mutations in metabolism genes in chronic liver disease. Nature 2021, 598: 473-478. PMID: 34646017, DOI: 10.1038/s41586-021-03974-6.Peer-Reviewed Original ResearchConceptsSomatic mutationsConvergent evolutionNon-alcoholic fatty liver diseaseMetabolic genesAlcohol-related liver diseaseFatty liver diseaseFrequent convergent evolutionRegulation of metabolic pathwaysLiver diseaseExcess of mutationsLipid droplet metabolismHepatocellular carcinomaBurden of somatic mutationsStorage triacylglycerolsAcquisition of somatic mutationsNuclear exportIndependent clonesChronic liver diseases to hepatocellular carcinomaIncreased clone sizePositive selectionMaster regulatorsTranscription factorsInsulin signalingChronic liver diseaseMetabolic pathwaysCTCF 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
2018
Optoacoustics delineates murine breast cancer models displaying angiogenesis and vascular mimicry
Quiros-Gonzalez I, Tomaszewski M, Aitken S, Ansel-Bollepalli L, McDuffus L, Gill M, Hacker L, Brunker J, Bohndiek S. Optoacoustics delineates murine breast cancer models displaying angiogenesis and vascular mimicry. British Journal Of Cancer 2018, 118: 1098-1106. PMID: 29576623, PMCID: PMC5931091, DOI: 10.1038/s41416-018-0033-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological MimicryBreast NeoplasmsCell Line, TumorDrug MonitoringFemaleHumansMammary Neoplasms, ExperimentalMCF-7 CellsMiceMice, Inbred BALB CMice, NudeNeoplasm StagingNeovascularization, PathologicOxygen ConsumptionPhotoacoustic TechniquesSensitivity and SpecificityTomographyTumor HypoxiaXenograft Model Antitumor AssaysConceptsMDA-MB-231Breast cancer modelCancer modelsVascular mimicryOrthotopic breast cancer xenograftsVascular phenotypeMurine breast cancer modelMDA-MB-231 tumorsMCF-7Consistent with angiogenesisMCF-7 tumorsTotal hemoglobinBreast cancer xenograftsBreast tumor modelEx vivo analysisNO serum levelsTumor oxygenationEstrogen-independentCancer xenograftsSerum levelsEstrogen-dependentTherapeutic responseBreast tumorsTumor modelClinical trials
2015
Next-generation sequencing is highly sensitive for the detection of beta-catenin mutations in desmoid-type fibromatoses
Aitken S, Presneau N, Kalimuthu S, Dileo P, Berisha F, Tirabosco R, Amary M, Flanagan A. Next-generation sequencing is highly sensitive for the detection of beta-catenin mutations in desmoid-type fibromatoses. Virchows Archiv 2015, 467: 203-210. PMID: 25838078, DOI: 10.1007/s00428-015-1765-0.Peer-Reviewed Original ResearchConceptsNext-generation sequencingRestriction enzyme digestionMutation-specific restriction enzyme digestionEnzyme digestionIon Torrent Personal Genome MachineDesmoid-type fibromatosesPersonal Genome MachineMutation detection techniquesSpecificity of next-generation sequencingPolymerase chain reaction amplificationPrimer pairsCTNNB1 mutationsMinimal DNAMutational hotspotsBeta-catenin mutationsDetected CTNNB1 mutationsBeta-cateninMutationsDNAParaffin-embedded needle biopsiesSequenceSpindle cell lesionsMultiplex assayRecurrent tumorsNeedle biopsy
2014
Mutations in IDH1 and IDH2 are not present in sporadic ovarian sex cord–stromal tumours
Aitken S, Presneau N, Khatri B, Flanagan A, Clarke B, McCluggage W. Mutations in IDH1 and IDH2 are not present in sporadic ovarian sex cord–stromal tumours. Histopathology 2014, 66: 897-898. PMID: 25040869, DOI: 10.1111/his.12489.Peer-Reviewed Original Research
2011
Accuracy of hepatocellular carcinoma detection on multidetector CT in a transplant liver population with explant liver correlation
Addley H, Griffin N, Shaw A, Mannelli L, Parker R, Aitken S, Wood H, Davies S, Alexander G, Lomas D. Accuracy of hepatocellular carcinoma detection on multidetector CT in a transplant liver population with explant liver correlation. Clinical Radiology 2011, 66: 349-356. PMID: 21295772, DOI: 10.1016/j.crad.2010.11.012.Peer-Reviewed Original ResearchConceptsDetection of HCC lesionsMultidetector computed tomographyHepatocellular carcinomaMDCT examinationsHCC lesionsLiver transplantationDiagnostic confidenceDiagnostic accuracyDiagnostic accuracy of multidetector computed tomographyAccuracy of multidetector computed tomographySize of hepatocellular carcinomaLesion sizeDetection of hepatocellular carcinomaFive-point confidence scaleHepatocellular carcinoma detectionHelical CT imagesEffect of radiologist experienceLiver populationMultidetector CTCirrhotic patientsHistopathological correlationHistopathological resultsComputed tomographyCarcinoma detectionRadiologist experience
2010
Reply to: Discordant expression of molecular markers between primary and nodal metastases: a histopathological manifestation of the ‘self (stem cell)-seeding’ nature of breast cancer disease?
Faratian D, Aitken S, Thomas J, Langdon S, Harrison D. Reply to: Discordant expression of molecular markers between primary and nodal metastases: a histopathological manifestation of the ‘self (stem cell)-seeding’ nature of breast cancer disease? Annals Of Oncology 2010, 21: 1375. PMID: 20215137, DOI: 10.1093/annonc/mdq046.Peer-Reviewed Original Research
2009
Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases
Aitken S, Thomas J, Langdon S, Harrison D, Faratian D. Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases. Annals Of Oncology 2009, 21: 1254-1261. PMID: 19858088, DOI: 10.1093/annonc/mdp427.Peer-Reviewed Original ResearchConceptsNodal diseaseReceptor statusPrimary tumorAdjuvant therapyHER2 expressionReceptor expressionInvasive primary breast carcinomasPaired lymph nodeQuantitative receptor expressionPrimary breast carcinomaPrimary breast cancerResistance to therapyExpression of molecular markersNodal metastasisBreast carcinomaLymph nodesTherapeutic resistanceBreast cancerQuantitative immunofluorescenceClinical trialsTumorImmunohistochemistryTherapyPatientsMolecular phenotypes