2023
Integrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma
Chong M, Knight J, Peng G, Ji W, Chai H, Lu Y, Wu S, Li P, Hu Q. Integrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma. Cancer Genetics 2023, 276: 30-35. PMID: 37418972, DOI: 10.1016/j.cancergen.2023.06.002.Peer-Reviewed Original ResearchConceptsTumor mutation burdenWhole-exome sequencingGrade IIIHepatocellular carcinomaCNA burdenCase seriesBarcelona Clinic Liver Cancer stageExome sequencingBCLC stage CLiver Cancer stageEdmondson-Steiner gradingLarge case seriesGenetic defectsHigher CNA burdenAdjacent nontumor tissuesΒ-catenin pathwayBetter prognosisClinicopathologic findingsPoor prognosisClinicopathologic classificationCancer stageSurvival statusMutation burdenStage CPrognostic prediction
2020
Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
Jin SC, Lewis SA, Bakhtiari S, Zeng X, Sierant MC, Shetty S, Nordlie SM, Elie A, Corbett MA, Norton BY, van Eyk CL, Haider S, Guida BS, Magee H, Liu J, Pastore S, Vincent JB, Brunstrom-Hernandez J, Papavasileiou A, Fahey MC, Berry JG, Harper K, Zhou C, Zhang J, Li B, Zhao H, Heim J, Webber DL, Frank MSB, Xia L, Xu Y, Zhu D, Zhang B, Sheth AH, Knight JR, Castaldi C, Tikhonova IR, López-Giráldez F, Keren B, Whalen S, Buratti J, Doummar D, Cho M, Retterer K, Millan F, Wang Y, Waugh JL, Rodan L, Cohen JS, Fatemi A, Lin AE, Phillips JP, Feyma T, MacLennan SC, Vaughan S, Crompton KE, Reid SM, Reddihough DS, Shang Q, Gao C, Novak I, Badawi N, Wilson YA, McIntyre SJ, Mane SM, Wang X, Amor DJ, Zarnescu DC, Lu Q, Xing Q, Zhu C, Bilguvar K, Padilla-Lopez S, Lifton RP, Gecz J, MacLennan AH, Kruer MC. Mutations disrupting neuritogenesis genes confer risk for cerebral palsy. Nature Genetics 2020, 52: 1046-1056. PMID: 32989326, PMCID: PMC9148538, DOI: 10.1038/s41588-020-0695-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCerebral PalsyCyclin DCytoskeletonDrosophilaExomeExome SequencingExtracellular MatrixF-Box ProteinsFemaleFocal AdhesionsGenetic Predisposition to DiseaseGenome, HumanHumansMaleMutationNeuritesRhoB GTP-Binding ProteinRisk FactorsSequence Analysis, DNASignal TransductionTubulinTumor Suppressor ProteinsConceptsDamaging de novo mutationsCerebral palsyDe novo mutationsCerebral palsy casesRisk genesDamaging de novoNovo mutationsWhole-exome sequencingPalsy casesNeuromotor functionD levelsMonogenic etiologyCyclin D levelsNeuronal connectivityPalsyGene confer riskConfer riskRecessive variantsNeurodevelopmental disorder genesReverse genetic screenDisorder genesParent-offspring triosGenome-wide significanceGenomic factorsCytoskeleton pathway
2019
Genomic sites hypersensitive to ultraviolet radiation
Premi S, Han L, Mehta S, Knight J, Zhao D, Palmatier MA, Kornacker K, Brash DE. Genomic sites hypersensitive to ultraviolet radiation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 24196-24205. PMID: 31723047, PMCID: PMC6883822, DOI: 10.1073/pnas.1907860116.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsCells, CulturedDNA DamageFibroblastsGene Expression RegulationGenome, HumanHigh-Throughput Nucleotide SequencingHumansMelanocytesMelanomaMutationPromoter Regions, GeneticProtein BiosynthesisPyrimidine DimersPyrimidine NucleotidesSkin NeoplasmsTOR Serine-Threonine KinasesUltraviolet RaysConceptsCyclobutane pyrimidine dimersETS family transcription factorsIndividual gene promotersFamily transcription factorsRNA-binding proteinPrimary human melanocytesSingle-base resolutionEpigenetic marksGenomic averageTranslation regulationGenomic sitesMotif locationsTranscription factorsCell physiologyGene promoterCancer driversGenomeHuman melanocytesCell typesTumor evolutionCell pathwaysRare mutationsUV targetPyrimidine dimersApurinic sites
2018
Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation
Duran D, Zeng X, Jin SC, Choi J, Nelson-Williams C, Yatsula B, Gaillard J, Furey CG, Lu Q, Timberlake AT, Dong W, Sorscher MA, Loring E, Klein J, Allocco A, Hunt A, Conine S, Karimy JK, Youngblood MW, Zhang J, DiLuna ML, Matouk CC, Mane S, Tikhonova IR, Castaldi C, López-Giráldez F, Knight J, Haider S, Soban M, Alper SL, Komiyama M, Ducruet AF, Zabramski JM, Dardik A, Walcott BP, Stapleton CJ, Aagaard-Kienitz B, Rodesch G, Jackson E, Smith ER, Orbach DB, Berenstein A, Bilguvar K, Vikkula M, Gunel M, Lifton RP, Kahle KT. Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation. Neuron 2018, 101: 429-443.e4. PMID: 30578106, PMCID: PMC10292091, DOI: 10.1016/j.neuron.2018.11.041.Peer-Reviewed Original ResearchConceptsChromatin modifiersVascular developmentSpecification of arteriesDeep venous systemNormal vascular developmentParent-offspring triosSignaling GenesGalen malformationDamaging mutationsGenesMutationsEssential roleArterio-venous malformationsCutaneous vascular abnormalitiesNovo mutationsExome sequencingDisease biologyIncomplete penetranceVariable expressivityVascular abnormalitiesVenous systemMutation carriersArterial bloodMutation burdenClinical implicationsDe Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus
Furey CG, Choi J, Jin SC, Zeng X, Timberlake AT, Nelson-Williams C, Mansuri MS, Lu Q, Duran D, Panchagnula S, Allocco A, Karimy JK, Khanna A, Gaillard JR, DeSpenza T, Antwi P, Loring E, Butler WE, Smith ER, Warf BC, Strahle JM, Limbrick DD, Storm PB, Heuer G, Jackson EM, Iskandar BJ, Johnston JM, Tikhonova I, Castaldi C, López-Giráldez F, Bjornson RD, Knight JR, Bilguvar K, Mane S, Alper SL, Haider S, Guclu B, Bayri Y, Sahin Y, Apuzzo MLJ, Duncan CC, DiLuna ML, Günel M, Lifton RP, Kahle KT. De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus. Neuron 2018, 99: 302-314.e4. PMID: 29983323, PMCID: PMC7839075, DOI: 10.1016/j.neuron.2018.06.019.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusNeural stem cell fateHuman congenital hydrocephalusDamaging de novoCerebrospinal fluid homeostasisSubstantial morbidityCH patientsTherapeutic ramificationsSignificant burdenBrain ventriclesCH pathogenesisNeural tube developmentFluid homeostasisDe novo mutationsExome sequencingAdditional probandsHydrocephalusPathogenesisNovo mutationsNovo duplicationProbandsDe novoCell fateMorbidityPatients
2017
Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands
Jin SC, Homsy J, Zaidi S, Lu Q, Morton S, DePalma SR, Zeng X, Qi H, Chang W, Sierant MC, Hung WC, Haider S, Zhang J, Knight J, Bjornson RD, Castaldi C, Tikhonoa IR, Bilguvar K, Mane SM, Sanders SJ, Mital S, Russell MW, Gaynor JW, Deanfield J, Giardini A, Porter GA, Srivastava D, Lo CW, Shen Y, Watkins WS, Yandell M, Yost HJ, Tristani-Firouzi M, Newburger JW, Roberts AE, Kim R, Zhao H, Kaltman JR, Goldmuntz E, Chung WK, Seidman JG, Gelb BD, Seidman CE, Lifton RP, Brueckner M. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nature Genetics 2017, 49: 1593-1601. PMID: 28991257, PMCID: PMC5675000, DOI: 10.1038/ng.3970.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutistic DisorderCardiac MyosinsCase-Control StudiesChildExomeFemaleGene ExpressionGenetic Predisposition to DiseaseGenome-Wide Association StudyGrowth Differentiation Factor 1Heart Defects, CongenitalHeterozygoteHigh-Throughput Nucleotide SequencingHomozygoteHumansMaleMutationMyosin Heavy ChainsPedigreeRiskVascular Endothelial Growth Factor Receptor-3
2015
Integrated genomic characterization of IDH1-mutant glioma malignant progression
Bai H, Harmancı AS, Erson-Omay EZ, Li J, Coşkun S, Simon M, Krischek B, Özduman K, Omay SB, Sorensen EA, Turcan Ş, Bakırcığlu M, Carrión-Grant G, Murray PB, Clark VE, Ercan-Sencicek AG, Knight J, Sencar L, Altınok S, Kaulen LD, Gülez B, Timmer M, Schramm J, Mishra-Gorur K, Henegariu O, Moliterno J, Louvi A, Chan TA, Tannheimer SL, Pamir MN, Vortmeyer AO, Bilguvar K, Yasuno K, Günel M. Integrated genomic characterization of IDH1-mutant glioma malignant progression. Nature Genetics 2015, 48: 59-66. PMID: 26618343, PMCID: PMC4829945, DOI: 10.1038/ng.3457.Peer-Reviewed Original ResearchConceptsDevelopmental transcription factorsActivation of MYCMalignant progressionGenomic approachesPI3K pathwayGlioma malignant progressionEpigenetic silencingIDH1 mutant gliomasTranscription factorsIntegrated genomic characterizationGenomic characterizationRTK-RASOncogenic pathwaysK pathwayClonal expansionPathwaySilencingMYCProgression