title: Single-nucleotide polymorphism-array improves detection rate of genomic alterations in core-binding factor leukemia.
abstract: Acute myeloid leukemia (AML) is a group of clonal diseases, resulting from two classes of mutation. Investigation for additional abnormalities associated with a well-recognized subtype, core-binding factor AML (CBF-AML) can provide further understanding and discrimination to this special group of leukemia. In order to better define genetic alterations in CBF-AML and identify possible cooperating lesions, a single-nucleotide polymorphism-array (SNP-array) analysis was performed, combined to KIT mutation screening, in a set of cases. Validation of SNP-array results was done by array comparative genomic hybridization and FISH. Fifteen cases were analyzed. Three cases had microscopic lesions better delineated by arrays. One case had +22 not identified by arrays. Submicroscopic abnormalities were mostly non-recurrent between samples. Of relevance, four regions were more frequently affected: 4q28, 9p11, 16q22.1, and 16q23. One case had an uncovered unbalanced inv(16) due to submicroscopic deletion of 5´MYH11 and 3´CBFB. Telomeric and large copy number neutral loss of heterozygosity (CNN-LOH) regions (>25 Mb), likely representing uniparental disomy, were detected in four out of fifteen cases. Only three cases had mutation on KIT gene, enhancing the role of abnormalities by SNP-array as presumptive cooperating alterations. Molecular karyotyping can add valuable information to metaphase karyotype analysis, emerging as an important tool to uncover and characterize microscopic, submicroscopic genomic alterations, and CNN-LOH events in the search for cooperating lesions.
authors: Division of Hematology and Hemotherapy, UNIFESP/Escola Paulista de Medicina, São Paulo, SP, CEP: 04037-002, Brazil. aninhabra@yahoo.com.br
authors: Ana Rosa da Silveira
authors: AR
authors: Costa
authors: Anupama
authors: A
authors: Vasudevan
authors: Ana
authors: A
authors: Krepischi
authors: Carla
authors: C
authors: Rosenberg
authors: Maria de Lourdes L F
authors: Mde L
authors: Chauffaille
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D050660:Core Binding Factors / Q000235:genetics*; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D050660:Core Binding Factors
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