2023
Toward Precision Oncology in Glioblastoma with a Personalized Cancer Genome Reporting Tool and Genetic Changes Identified by Whole Exome Sequencing
Erdogan O, Özkaya Ş, Erzik C, Bilguvar K, Arga K, Bayraklı F. Toward Precision Oncology in Glioblastoma with a Personalized Cancer Genome Reporting Tool and Genetic Changes Identified by Whole Exome Sequencing. OMICS A Journal Of Integrative Biology 2023, 27: 426-433. PMID: 37669106, DOI: 10.1089/omi.2023.0117.Peer-Reviewed Original ResearchMeSH KeywordsDNA Copy Number VariationsExome SequencingGlioblastomaHumansPhosphatidylinositol 3-KinasesPrecision MedicineConceptsTreatment optionsWhole-exome sequencingPrecision/personalized medicineExome sequencingLimited treatment optionsGenetic alterationsPersonalized medicinePotential therapeutic targetAggressive brain tumorTumor tissue samplesPoor prognosisGBM patientsTargetable pathwaysBrain tumorsTherapeutic targetLarger studyMolecular findingsNeurosurgical oncologyGenomic profilingPatientsPersonalized therapyMolecular profilingAkt/GlioblastomaPrecision oncology
2021
Sequential filtering for clinically relevant variants as a method for clinical interpretation of whole exome sequencing findings in glioma
Ülgen E, Can Ö, Bilguvar K, Akyerli Boylu C, Kılıçturgay Yüksel Ş, Erşen Danyeli A, Sezerman OU, Yakıcıer MC, Pamir MN, Özduman K. Sequential filtering for clinically relevant variants as a method for clinical interpretation of whole exome sequencing findings in glioma. BMC Medical Genomics 2021, 14: 54. PMID: 33622343, PMCID: PMC7903763, DOI: 10.1186/s12920-021-00904-3.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorDNA Copy Number VariationsExome SequencingGenomicsHumansNeoplasm Recurrence, LocalConceptsTumor mutational burdenSomatic copy number alterationsWhole-exome sequencing findingsMicrosatellite instabilityGermline variantsClinical interpretationIndividual brain tumorsShort variantRecurrent tumorsMSI incidenceMutational burdenBrain tumorsLoss of heterozygosityPathway enrichment analysisPrimary gliomasClinical settingTumorsWES analysisCopy number alterationsTumor samplesSequencing findingsDiffuse gliomasClinical analysisGliomasChr10 loss
2020
Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome
Dyment DA, O'Donnell‐Luria A, Agrawal PB, Akdemir Z, Aleck KA, Antaki D, Al Sharhan H, Au P, Aydin H, Beggs AH, Bilguvar K, Boerwinkle E, Brand H, Brownstein CA, Buyske S, Chodirker B, Choi J, Chudley AE, Clericuzio CL, Cox GF, Curry C, de Boer E, de Vries B, Dunn K, Dutmer CM, England EM, Fahrner JA, Geckinli BB, Genetti CA, Gezdirici A, Gibson WT, Gleeson JG, Greenberg CR, Hall A, Hamosh A, Hartley T, Jhangiani SN, Karaca E, Kernohan K, Lauzon JL, Lewis MES, Lowry RB, López‐Giráldez F, Matise TC, McEvoy‐Venneri J, McInnes B, Mhanni A, Minaur S, Moilanen J, Nguyen A, Nowaczyk MJM, Posey JE, Õunap K, Pehlivan D, Pajusalu S, Penney LS, Poterba T, Prontera P, Doriqui MJR, Sawyer SL, Sobreira N, Stanley V, Torun D, Wargowski D, Witmer PD, Wong I, Xing J, Zaki MS, Zhang Y, Consortium C, Genomics C, Boycott KM, Bamshad MJ, Nickerson DA, Blue EE, Innes AM. Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome. American Journal Of Medical Genetics Part A 2020, 185: 119-133. PMID: 33098347, PMCID: PMC8197629, DOI: 10.1002/ajmg.a.61926.Peer-Reviewed Original ResearchConceptsGenome sequencingExtensive locus heterogeneityCopy number variationsGenomic analysisMolecular diagnosisSingle geneDe novo variantsNext-generation sequencingDisease genesWide sequencingGenesGenomic diagnosisLocus heterogeneityNovo variantsSequencingPhenotypeAdditional familiesBiallelic variantsHDAC8FamilyVariant filteringDistinctive facial appearanceClinical phenotypeVariantsUncertain significance
2019
Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patients
2016
Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports
Brownstein CA, Kleiman RJ, Engle EC, Towne MC, D'Angelo EJ, Yu TW, Beggs AH, Picker J, Fogler JM, Carroll D, Schmitt RC, Wolff RR, Shen Y, Lip V, Bilguvar K, Kim A, Tembulkar S, O'Donnell K, Gonzalez-Heydrich J. Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports. American Journal Of Medical Genetics Part A 2016, 170: 1165-1173. PMID: 26887912, PMCID: PMC4833544, DOI: 10.1002/ajmg.a.37595.Peer-Reviewed Original ResearchA patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP
Çağlayan AO, Tüysüz B, Coşkun S, Quon J, Harmancı AS, Baranoski JF, Baran B, Erson-Omay EZ, Henegariu O, Mane SM, Bilgüvar K, Yasuno K, Günel M. A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP. Journal Of Human Genetics 2016, 61: 395-403. PMID: 26740239, PMCID: PMC4880488, DOI: 10.1038/jhg.2015.160.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-Ketoglutarate-Dependent Dioxygenase FTOApoptosisBiopsyChild, PreschoolCholesterol Ester Transfer ProteinsComputational BiologyConsanguinityDNA Copy Number VariationsDNA Mutational AnalysisExomeFemaleGene ExpressionGene Expression ProfilingGenetic Association StudiesGenotypeHigh-Throughput Nucleotide SequencingHomozygoteHumansMutation, MissensePhenotypeTranscriptome
2015
Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis
Erson-Omay EZ, Çağlayan AO, Schultz N, Weinhold N, Omay SB, Özduman K, Köksal Y, Li J, Serin Harmancı A, Clark V, Carrión-Grant G, Baranoski J, Çağlar C, Barak T, Coşkun S, Baran B, Köse D, Sun J, Bakırcıoğlu M, Moliterno Günel J, Pamir MN, Mishra-Gorur K, Bilguvar K, Yasuno K, Vortmeyer A, Huttner AJ, Sander C, Günel M. Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis. Neuro-Oncology 2015, 17: 1356-1364. PMID: 25740784, PMCID: PMC4578578, DOI: 10.1093/neuonc/nov027.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasSomatic POLE mutationsPOLE mutationsMalignant high-grade gliomasLonger progression-free survivalProgression-free survivalSomatic mutationsOverall survivalPediatric patientsBetter prognosisClinical featuresImproved prognosisClinical behaviorImmune cellsBizarre cellsAggressive formGlioblastoma multiformeDisease pathophysiologyMolecular subgroupsHomozygous germline mutationGermline mutationsPrognosisGlioma subtypesComprehensive genomic analysisDistinct subgroups
2011
Rare Copy Number Variants in Tourette Syndrome Disrupt Genes in Histaminergic Pathways and Overlap with Autism
Fernandez TV, Sanders SJ, Yurkiewicz IR, Ercan-Sencicek AG, Kim YS, Fishman DO, Raubeson MJ, Song Y, Yasuno K, Ho WS, Bilguvar K, Glessner J, Chu SH, Leckman JF, King RA, Gilbert DL, Heiman GA, Tischfield JA, Hoekstra PJ, Devlin B, Hakonarson H, Mane SM, Günel M, State MW. Rare Copy Number Variants in Tourette Syndrome Disrupt Genes in Histaminergic Pathways and Overlap with Autism. Biological Psychiatry 2011, 71: 392-402. PMID: 22169095, PMCID: PMC3282144, DOI: 10.1016/j.biopsych.2011.09.034.Peer-Reviewed Original ResearchConceptsCopy number variationsRare copy number variationsNovel risk regionsEnrichment of genesGamma-aminobutyric acid receptor genesNervous system developmentEtiology of TSParent-child triosRare copy number variantsCopy number variantsGene mappingPathway analysisDe novo eventsAxon guidanceCell adhesionMolecular pathwaysNumber variationsRelevant pathwaysCNV analysisNumber variantsGenesReceptor geneDe novoNovo eventsPathwayMultiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism
Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT, Moreno-De-Luca D, Chu SH, Moreau MP, Gupta AR, Thomson SA, Mason CE, Bilguvar K, Celestino-Soper PB, Choi M, Crawford EL, Davis L, Wright NR, Dhodapkar RM, DiCola M, DiLullo NM, Fernandez TV, Fielding-Singh V, Fishman DO, Frahm S, Garagaloyan R, Goh GS, Kammela S, Klei L, Lowe JK, Lund SC, McGrew AD, Meyer KA, Moffat WJ, Murdoch JD, O'Roak BJ, Ober GT, Pottenger RS, Raubeson MJ, Song Y, Wang Q, Yaspan BL, Yu TW, Yurkiewicz IR, Beaudet AL, Cantor RM, Curland M, Grice DE, Günel M, Lifton RP, Mane SM, Martin DM, Shaw CA, Sheldon M, Tischfield JA, Walsh CA, Morrow EM, Ledbetter DH, Fombonne E, Lord C, Martin CL, Brooks AI, Sutcliffe JS, Cook EH, Geschwind D, Roeder K, Devlin B, State MW. Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism. Neuron 2011, 70: 863-885. PMID: 21658581, PMCID: PMC3939065, DOI: 10.1016/j.neuron.2011.05.002.Peer-Reviewed Original ResearchAdolescentCadherinsCalcium-Binding ProteinsCell Adhesion Molecules, NeuronalChildChild Development Disorders, PervasiveChild, PreschoolChromosomes, Human, Pair 16Chromosomes, Human, Pair 7Chromosomes, Human, XDNA Copy Number VariationsFamily HealthFemaleGene DuplicationGene Expression ProfilingGenome-Wide Association StudyGenotypeHumansMaleNerve Tissue ProteinsNeural Cell Adhesion MoleculesOligonucleotide Array Sequence AnalysisPhenotypeProteinsSiblingsUbiquitin ThiolesteraseUbiquitin-Specific Peptidase 7Williams Syndrome
2009
The syndrome of pachygyria, mental retardation, and arachnoid cysts maps to 11p15
Bilguvar K, Ozturk AK, Bayrakli F, Guzel A, DiLuna ML, Bayri Y, Tatli M, Tekes S, Arlier Z, Yasuno K, Mason CE, Lifton RP, State MW, Gunel M. The syndrome of pachygyria, mental retardation, and arachnoid cysts maps to 11p15. American Journal Of Medical Genetics Part A 2009, 149A: 2569-2572. PMID: 19876906, DOI: 10.1002/ajmg.a.33063.Peer-Reviewed Original ResearchAbnormalities, MultipleArachnoid CystsBlood Specimen CollectionChromosome MappingChromosomes, Human, Pair 11DNADNA Copy Number VariationsFamilyFemaleGenome, HumanGenome-Wide Association StudyGenotypeHomozygoteHumansIntellectual DisabilityLissencephalyLod ScoreMalePedigreePhenotypePolymorphism, Single NucleotideSyndrome