title: Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease.
abstract: The age-specific differences in the genetic mechanisms of myeloid leukemogenesis have been observed and studied previously. However, NGS technology has provided a possibility to obtain a large amount of mutation data. We analyzed DNA samples from 20 childhood (cAML) and 20 adult AML (aAML) patients, using NGS targeted sequencing. The average coverage of high-quality sequences was 2981 × per amplicon. A total of 412 (207 cAML, 205 aAML) variants in the coding regions were detected; out of which, only 122 (62 cAML and 60 aAML) were potentially protein-changing. Our results confirmed that AML contains small number of genetic alterations (median 3 mutations/patient in both groups). The prevalence of the most frequent single gene AML associated mutations differed in cAML and aAML patient cohorts: IDH1 (0 % cAML, 5 % aAML), IDH2 (0 % cAML, 10 % aAML), NPM1 (10 % cAML, 35 % aAML). Additionally, potentially protein-changing variants were found in tyrosine kinase genes or genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) in cAML, while among aAML, the prevalence is directed towards variants in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1). Besides uniform genomic profile of AML, specific genetic characteristic was exclusively detected in cAML and aAML.
authors.affiliation: Laboratory for Molecular Biomedicine, Institute for Molecular Genetica and Genetic Engineering University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia.
authors.forename: Irena
authors.initials: I
authors.lastname: Marjanovic
authors.affiliation: Laboratory for Molecular Biomedicine, Institute for Molecular Genetica and Genetic Engineering University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Kostic
authors.affiliation: Laboratory for Molecular Biomedicine, Institute for Molecular Genetica and Genetic Engineering University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Stanic
authors.affiliation: Laboratory for Molecular Biomedicine, Institute for Molecular Genetica and Genetic Engineering University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia.
authors.forename: Nadja
authors.initials: N
authors.lastname: Pejanovic
authors.affiliation: Laboratory for Molecular Biomedicine, Institute for Molecular Genetica and Genetic Engineering University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Lucic
authors.affiliation: Laboratory for Molecular Biomedicine, Institute for Molecular Genetica and Genetic Engineering University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia.
authors.forename: Teodora
authors.initials: T
authors.lastname: Karan-Djurasevic
authors.affiliation: University Children's Hospital, Belgrade, Serbia.|School of Medicine University of Belgrade, Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Janic
authors.affiliation: University Children's Hospital, Belgrade, Serbia.|School of Medicine University of Belgrade, Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Dokmanovic
authors.affiliation: University Children's Hospital, Belgrade, Serbia.
authors.forename: Srdja
authors.initials: S
authors.lastname: Jankovic
authors.affiliation: School of Medicine University of Belgrade, Belgrade, Serbia.|Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Nada Suvajdzic
authors.initials: NS
authors.lastname: Vukovic
authors.affiliation: School of Medicine University of Belgrade, Belgrade, Serbia.|Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Dragica
authors.initials: D
authors.lastname: Tomin
authors.affiliation: Seven Bridges Genomics, Belgrade, Serbia.
authors.forename: Ognjen
authors.initials: O
authors.lastname: Perisic
authors.affiliation: Seven Bridges Genomics, Belgrade, Serbia.
authors.forename: Goran
authors.initials: G
authors.lastname: Rakocevic
authors.affiliation: Seven Bridges Genomics, Belgrade, Serbia.
authors.forename: Milos
authors.initials: M
authors.lastname: Popovic
authors.affiliation: Laboratory for Molecular Biomedicine, Institute for Molecular Genetica and Genetic Engineering University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlovic
authors.affiliation: Laboratory for Molecular Biomedicine, Institute for Molecular Genetica and Genetic Engineering University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia. nmtosic@sezampro.rs.
authors.forename: Natasa
authors.initials: N
authors.lastname: Tosic
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D019295:Computational Biology; D005260:Female; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D011379:Prognosis; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D000090243:Nucleophosmin
keywords: Adult AML; Childhood AML; Next generation sequencing; SNVs