title: ETV6-RUNX1 fusion gene and additional genetic changes in infant leukemia: a genome-wide analysis.
abstract: Acute lymphoblastic leukemia (ALL) in infants is characterized by a high frequency of MLL gene rearrangements. By contrast, the t(12;21) ETV6-RUNX1 fusion gene is typically detected in children older than 2 years. In a series of Brazilian infant leukemia cases, however, four younger cases harbored ETV6-RUNX1, at ages 2, 3, 5, and 7 months. This finding could represent a unique model for delineating the additional genomic hits required to accelerate the emergence of a frank leukemia in these t(12;21)-positive cases. We applied a whole-genome copy number analysis with single-nucleotide polymorphism (SNP) arrays, comparing t(12;21) infants with older pediatric age groups. Recurrent deletions, including 9p21.3 (CDKN2A, CKDN2B, and MTAP), 11p13 (CD44), 12p13.2 (ETV6), and patient-specific abnormalities were identified. Although infant cases with t(12;21) did not display specific genetic abnormalities explaining the short latency to overt leukemia, the frequency of copy number abnormalities increased proportionally with age. This novel SNP array analysis in an extremely rare series of cases opens new ideas about the etiology of ETV6-RUNX1-positive ALL.
authors: Pediatric Hematology-Oncology Program, National Cancer Institute, INCA, Rua André Cavalcanti, 37, 20231-050 Rio de Janeiro, RJ, Brazil.
authors: Mariana
authors: M
authors: Emerenciano
authors: Silvia
authors: S
authors: Bungaro
authors: Giovanni
authors: G
authors: Cazzaniga
authors: Maria Dolores Fonseca
authors: MD
authors: Dorea
authors: Virginia Maria
authors: VM
authors: Coser
authors: Isis Quezado
authors: IQ
authors: Magalhães
authors: Andrea
authors: A
authors: Biondi
authors: Maria S
authors: MS
authors: Pombo-de-Oliveira
mesh_terms: D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D050939:Gene Fusion; D055106:Genome-Wide Association Study; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein