Featured Publications
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 carcinomaDeaminationVariantsPremetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma
Fisk JN, Mahal AR, Dornburg A, Gaffney SG, Aneja S, Contessa JN, Rimm D, Yu JB, Townsend JP. Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma. Cancer Letters 2021, 526: 346-351. PMID: 34780851, PMCID: PMC8702484, DOI: 10.1016/j.canlet.2021.11.011.Peer-Reviewed Original ResearchConceptsMutational processesSingle ancestral lineageAncestral lineageProgression of cancerMetastatic lineagesPhylogenetic analysisGenetic resistanceEvolutionary processesExogenous mutational processesCancer evolutionConsolidative therapyMutational signature analysisEGFR-positive non-small cell lung cancerNon-small cell lung cancerKey eventsLineagesCell populationsTherapeutic resistanceLocal consolidative therapyClinical time courseCell lung cancerDisease etiologyTherapeutic decision makingCisplatin therapyLung cancerHeavy mutagenesis by tobacco leads to lung adenocarcinoma tumors with KRAS G12 mutations other than G12D, leading KRAS G12D tumors—on average—to exhibit a lower mutation burden
Tan C, Mandell JD, Dasari K, Cannataro VL, Alfaro-Murillo JA, Townsend JP. Heavy mutagenesis by tobacco leads to lung adenocarcinoma tumors with KRAS G12 mutations other than G12D, leading KRAS G12D tumors—on average—to exhibit a lower mutation burden. Lung Cancer 2021, 166: 265-269. PMID: 34736794, DOI: 10.1016/j.lungcan.2021.10.008.Peer-Reviewed Original ResearchEstimation of neutral mutation rates and quantification of somatic variant selection using canceffectsizeR
Mandell J, Cannataro V, Townsend J. Estimation of neutral mutation rates and quantification of somatic variant selection using canceffectsizeR. Cancer Research 2022, 83: 500-505. PMID: 36469362, PMCID: PMC9929515, DOI: 10.1158/0008-5472.can-22-1508.Peer-Reviewed Original ResearchConceptsMutation rateEpistatic effectsSite-specific mutation ratesNeutral mutation rateNucleotide mutation ratePan-cancer datasetCancer cell survivalFunctional impact scoresCustom genomesPairwise epistasisSet of variantsHuman genomeR packageTranscriptomic dataSomatic variant dataModel of selectionSingle nucleotideCancer effectsCell survivalNucleotide mutationsCancer biologyVariant dataMutational signature analysisMutationsSomatic mutations
2022
A phylogenetic approach to study the evolution of somatic mutational processes in cancer
Miura S, Vu T, Choi J, Townsend JP, Karim S, Kumar S. A phylogenetic approach to study the evolution of somatic mutational processes in cancer. Communications Biology 2022, 5: 617. PMID: 35732905, PMCID: PMC9217972, DOI: 10.1038/s42003-022-03560-0.Peer-Reviewed Original ResearchConceptsMutational processesPattern of conservationFalse-positive discovery rateCollection of mutationsSomatic mutational processesPhylogenetic approachGenomic variationSomatic variationCell lineagesMutational signaturesTumor evolutionMutation signaturesPhylogenyCancer cellsDiscovery rateMutationsComputer-simulated datasetsRelative activityLineagesComputational methodsSignaturesConservationDivergenceEvolutionJoint analysis
2020
Comparative Genomics within and across Bilaterians Illuminates the Evolutionary History of ALK and LTK Proto-Oncogene Origination and Diversification
Dornburg A, Wang Z, Wang J, Mo ES, López-Giráldez F, Townsend JP. Comparative Genomics within and across Bilaterians Illuminates the Evolutionary History of ALK and LTK Proto-Oncogene Origination and Diversification. Genome Biology And Evolution 2020, 13: evaa228. PMID: 33196781, PMCID: PMC7851593, DOI: 10.1093/gbe/evaa228.Peer-Reviewed Original ResearchConceptsLeukocyte tyrosine kinaseEvolutionary historyPhylogenetic analysisProtein-coding genesComparative genomic analysisEarly embryonic expressionMetazoan genomesComparative genomicsPhylogenetic contextModel organismsEmbryonic expressionModel speciesHuman genesKey genesGenomic analysisImportant genesMammal systemsFunctional convergenceTyrosine kinaseMolecular homologyGenesFunctional roleVertebratesMammal modelsHomology
2017
Radiation-Specific Clinical Data Should Be Included in Existing Large-Scale Genomic Datasets
Chen WS, Townsend JP, Yu JB. Radiation-Specific Clinical Data Should Be Included in Existing Large-Scale Genomic Datasets. International Journal Of Radiation Oncology • Biology • Physics 2017, 98: 8-10. PMID: 28587055, DOI: 10.1016/j.ijrobp.2017.01.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsWhole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up
Kadara H, Choi M, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Yoo Y, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Wistuba II, Herbst RS. Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up. Annals Of Oncology 2017, 28: 75-82. PMID: 27687306, PMCID: PMC5982809, DOI: 10.1093/annonc/mdw436.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalPoor recurrence-free survivalWhole-exome sequencingEarly-stage lung adenocarcinomaMutant lung adenocarcinomaLung adenocarcinomaImmune markersClinical outcomesExact testNatural killer cell infiltrationProportional hazards regression modelsGranzyme B levelsImmune marker analysisImmune profiling analysisPD-L1 expressionImmune-based therapiesTumoral PD-L1Hazards regression modelsKRAS mutant tumorsNormal lung tissuesMajority of deathsFisher's exact testHigh mutation burdenAnalysis of immunophenotypeRelevant molecular markersMutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function
Choi M, Kadara H, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Kim K, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Herbst RS, Wistuba II. Mutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function. Annals Of Oncology 2017, 28: 83-89. PMID: 28177435, PMCID: PMC6246501, DOI: 10.1093/annonc/mdw437.Peer-Reviewed Original ResearchConceptsLung squamous cell carcinomaEarly stage lung squamous cell carcinomaNon-small cell lung cancerSquamous cell carcinomaWhole-exome sequencingImmune markersClinical outcomesCell carcinomaPIK3CA mutationsExact testPoor recurrence-free survivalProportional hazards regression modelsTumoral PD-L1 expressionPD-L1 expressionRecurrence-free survivalCell lung cancerComprehensive immune profilingTP53 mutant tumorsHazards regression modelsNormal lung tissuesFisher's exact testLUSC cohortAdjuvant therapyImmune profilingPoor prognosis