ETV6-RUNX1 fusion gene and additional genetic changes in infant leukemia: a genome-wide analysis.
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.
Emerenciano
Mariana
M
Pediatric Hematology-Oncology Program, National Cancer Institute, INCA, Rua André Cavalcanti, 37, 20231-050 Rio de Janeiro, RJ, Brazil.
Bungaro
Silvia
S
Cazzaniga
Giovanni
G
Dorea
Maria Dolores Fonseca
MD
Coser
Virginia Maria
VM
Magalhães
Isis Quezado
IQ
Biondi
Andrea
A
Pombo-de-Oliveira
Maria S
MS
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
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein