2025
APOBEC affects tumor evolution and age at onset of lung cancer in smokers
Zhang T, Sang J, Hoang P, Zhao W, Rosenbaum J, Johnson K, Klimczak L, McElderry J, Klein A, Wirth C, Bergstrom E, Díaz-Gay M, Vangara R, Colon-Matos F, Hutchinson A, Lawrence S, Cole N, Zhu B, Przytycka T, Shi J, Caporaso N, Homer R, Pesatori A, Consonni D, Imielinski M, Chanock S, Wedge D, Gordenin D, Alexandrov L, Harris R, Landi M. APOBEC affects tumor evolution and age at onset of lung cancer in smokers. Nature Communications 2025, 16: 4711. PMID: 40394004, PMCID: PMC12092836, DOI: 10.1038/s41467-025-59923-8.Peer-Reviewed Original ResearchConceptsLung cancerTumor evolutionMulti-omics profilingLung tumor samplesCell of originProgenitor-like cellsMulti-OmicsMutagenic processesMutational processesOff-target activityTP53 mutationsMutational burdenSignaling pathwayKRAS mutationsMutagenesisAPOBEC mutagenesisSomatic mutationsSolid tumorsTumor samplesClonal expansionDNA damageTumor developmentCell typesMutationsStemness markers
2022
APOBEC mutagenesis and selection for NFE2L2 contribute to the origin of lung squamous-cell carcinoma
Cannataro VL, Kudalkar S, Dasari K, Gaffney SG, Lazowski HM, Jackson LK, Yildiz I, Das RK, Rothberg BE, Anderson KS, Townsend JP. APOBEC mutagenesis and selection for NFE2L2 contribute to the origin of lung squamous-cell carcinoma. Lung Cancer 2022, 171: 34-41. PMID: 35872531, PMCID: PMC10126952, DOI: 10.1016/j.lungcan.2022.07.004.Peer-Reviewed Original ResearchConceptsCytidine deaminationMutagenic processesDefective homologous recombinationGenomic sequencesHomologous recombinationAttractive potential targetAPOBEC mutagenesisLung squamous cell carcinomaDeamination activityCancer cell growthAPOBEC proteinsAPOBEC activityCell growthCellular proliferationNFE2L2MutationsMolecular investigationsCancer effectsPotential targetMolecular variantsAPOBECSurvival of cancerSquamous cell carcinomaDeaminationVariants
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
2019
APOBEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma
Cannataro VL, Gaffney SG, Sasaki T, Issaeva N, Grewal NKS, Grandis JR, Yarbrough WG, Burtness B, Anderson KS, Townsend JP. APOBEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma. Oncogene 2019, 38: 3475-3487. PMID: 30647454, PMCID: PMC6499643, DOI: 10.1038/s41388-018-0657-6.Peer-Reviewed Original ResearchConceptsPositive selectionCancer phenotypeStrong positive selectionIntensity of selectionEffects of mutationsBasis of mutationsSomatic genetic variantsSomatic evolutionNeutral driftMutational processesAPOBEC mutagenesisBiochemical experimentsSelection intensityMolecular understandingCytosine basesIndividual substitutionsAPOBEC3B proteinMutant stateMutational signaturesGenetic variantsNeck squamous cell carcinomaMutationsE545KGene variantsPhenotype
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