Frequency of copy number abnormalities in common genes associated with B-cell precursor acute lymphoblastic leukemia cytogenetic subtypes in Brazilian children.
Copy number alterations (CNAs) in genes committed to B-cell precursors have been associated with poor survival in subgroups of patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). We investigated submicroscopic alterations in a series of 274 Brazilian children with BCP-ALL by multiplex ligation-dependent probe amplification and evaluated their correlation with clinical and laboratory features. The relevance of overlapping CNA abnormalities was also explored. Deletions/amplifications in at least one gene were identified in 83% of the total series. In children older than 2 years, there was a predominance of CNAs involving deletions in IKZF1, CDKN2A, and CDKN2B, whereas the pseudoautosomal region 1 (PAR1) had deletions that were found more frequently in infants (P <0.05). Based on the cytogenetic subgroups, favorable cytogenetic subgroups showed more deletions than other subgroups that occurred simultaneously, specifically ETV6 deletions (P <0.05). TCF3-PBX1 was frequently deleted in RB1, and an absence of deletions was observed in IKZF1 and genes localized to the PAR1 region. The results corroborate with previous genome-wide studies and aggregate new markers for risk stratification of BCP-ALL in Brazil.
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Thayana Conceição
TC
Barbosa
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Eugenia
E
Terra-Granado
Hospital da Criança José Alencar, Brasília, Brazil.
Isis M
IM
Quezado Magalhães
Hospital Sarina Rolin, São Paulo, Brazil.
Gustavo Ribeiro
GR
Neves
Hospital Napoleão Laureano, Paraíba, Brazil.
Andrea
A
Gadelha
Instituto de Hematologia da Paraíba, Paraíba, Brazil.
Gilson Espinola
GE
Guedes Filho
Hospital Regional de Mato Grosso do Sul, Mato Grosso do Sul, Brazil.
Marcelo Santos
MS
Souza
Hospital Santa Marcelina, São Paulo, Brazil.
Renato
R
Melaragno
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Mariana
M
Emerenciano
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. Electronic address: masocspoliveira@gmail.com.
Maria S
MS
Pombo-de-Oliveira
D000293:Adolescent; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D020732:Cytogenetic Analysis / Q000379:methods; D005784:Gene Amplification; D017353:Gene Deletion; D018628:Gene Dosage; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007223:Infant; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology
D005819:Genetic Markers
Acute lymphoblastic leukemia; IKZF1; MLPA; copy number alterations; multiplex ligation-dependent probe amplification