Featured Publications
Strand-resolved mutagenicity of DNA damage and repair
Anderson C, Talmane L, Luft J, Connelly J, Nicholson M, Verburg J, Pich O, Campbell S, Giaisi M, Wei P, Sundaram V, Connor F, Ginno P, Sasaki T, Gilbert D, López-Bigas N, Semple C, Odom D, Aitken S, Taylor M. Strand-resolved mutagenicity of DNA damage and repair. Nature 2024, 630: 744-751. PMID: 38867042, PMCID: PMC11186772, DOI: 10.1038/s41586-024-07490-1.Peer-Reviewed Original ResearchConceptsDNA damageDNA damage-induced mutationsSingle-base resolutionCancer genome evolutionDamage-induced mutationsRepair of DNA damageNucleotide excision repairGenome evolutionMultiple distinct mutationsDNA accessibilityGenomic conditionsReplicative strandProcess genomesDNA base damageTranslesion polymerasesExcision repairDNAMutation patternsMutationsBase damageRepair efficiencyStrandsAlkyl adductsReplicationIdentity fidelityDNA lesion bypass and the stochastic dynamics of transcription-coupled repair
Nicholson M, Anderson C, Odom D, Aitken S, Taylor M. DNA lesion bypass and the stochastic dynamics of transcription-coupled repair. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2403871121. PMID: 38717857, PMCID: PMC11098089, DOI: 10.1073/pnas.2403871121.Peer-Reviewed Original ResearchConceptsTranscription-coupled repairRNA polymerase IIDistribution of mutationsStalling of RNA polymerase IITranscription-coupled repair (TCRDNA damageGene expressionBarriers to gene expressionSites of DNA damageGenome-wide distributionBarrier to transcriptionDamaged DNA strandMammalian model systemsDNA lesion bypassGene bodiesPolymerase IIRNA polymeraseGenetic integrityGene productsDNA base damageLesion bypassAlkylation damageDNA strandsBypass lesionsMutationsSingle-mitosis dissection of acute and chronic DNA mutagenesis and repair
Ginno P, Borgers H, Ernst C, Schneider A, Behm M, Aitken S, Taylor M, Odom D. Single-mitosis dissection of acute and chronic DNA mutagenesis and repair. Nature Genetics 2024, 56: 913-924. PMID: 38627597, PMCID: PMC11096113, DOI: 10.1038/s41588-024-01712-y.Peer-Reviewed Original ResearchConceptsMutational processesUV damageGenome evolutionGenome-wideTranscribed regionsGenome replicationCancer genomesUV mutationCC dinucleotidesDNA mutagenesisSister cellsDriving evolutionGenomeMutagenesisPunctuated burstsSingle cellsRounds of genome replicationMutationsStrandsCellsMitosisDinucleotideSisterROSReplicationConvergent 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 pathwaysPervasive 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 pairsMutationsCellsGenomeSomatic mutations and clonal dynamics in healthy and cirrhotic human liver
Brunner S, Roberts N, Wylie L, Moore L, Aitken S, Davies S, Sanders M, Ellis P, Alder C, Hooks Y, Abascal F, Stratton M, Martincorena I, Hoare M, Campbell P. Somatic mutations and clonal dynamics in healthy and cirrhotic human liver. Nature 2019, 574: 538-542. PMID: 31645727, PMCID: PMC6837891, DOI: 10.1038/s41586-019-1670-9.Peer-Reviewed Original ResearchConceptsChronic liver diseaseHepatocellular carcinomaLiver diseaseCirrhotic liverMutational burdenSomatic mutationsMutational signaturesProgression to chronic liver diseaseSynchronous hepatocellular carcinomaNon-malignant hepatocytesExcessive alcohol intakeComplexity of hepatocellular carcinomaBands of fibrosisNon-alcoholic fatty liver diseaseStructural variantsFatty liver diseaseGenome of hepatocellular carcinomaClinical spectrumAlcohol intakeLiver failureViral hepatitisClonal expansionMalignant transformationHealth to diseaseRegenerative nodulesMutational landscape of a chemically-induced mouse model of liver cancer
Connor F, Rayner T, Aitken S, Feig C, Lukk M, Santoyo-Lopez J, Odom D. Mutational landscape of a chemically-induced mouse model of liver cancer. Journal Of Hepatology 2018, 69: 840-850. PMID: 29958939, PMCID: PMC6142872, DOI: 10.1016/j.jhep.2018.06.009.Peer-Reviewed Original ResearchConceptsSomatic single nucleotide variantsCarcinogen-induced mouse modelsModel of hepatocellular carcinomaMouse model of liver cancerMutational landscape of tumorsModel of liver cancerLandscape of tumorsHepatocellular carcinomaMouse modelMutational landscapeLiver cancerOncogenic drivers of HCCLiver tumorsNon-synonymous point mutationsGenomic alterationsHuman diseasesTruncating mutations of APCMutational signaturesMouse model of hepatocellular carcinomaSingle nucleotide variantsDrivers of hepatocellular carcinomaChemically-induced mouse modelCopy number alterationsCOSMIC mutational signaturesActivating hotspot mutations
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
An NRAS mutation in a case of Erdheim–Chester disease
Aitken S, Presneau N, Tirabosco R, Amary M, O'Donnell P, Flanagan A. An NRAS mutation in a case of Erdheim–Chester disease. Histopathology 2014, 66: 316-319. PMID: 24754681, DOI: 10.1111/his.12443.Peer-Reviewed Original ResearchMutations 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