Copy Number Alterations Associated with Acute Lymphoblastic Leukemia in Mexican Children. A report from The Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia

Abstract

B-cell precursor acute lymphocytic leukemia (B-ALL) represents a worldwide public health issue. Particularly, Mexico is one of the countries with the highest incidence of ALL in children. Between the multiple factors involved in ALL etiology, genetic alterations are clearly one of the most relevant features. In this work, a group of 24 B-ALL patients, all negative for the four most frequent gene fusions (ETV6-RUNX1, BCR-ABL1, TCF3-PBX1 and MLL-AF4), were included in a high-resolution microarray analysis in order to evaluate genomic copy-number alterations (CNAs). The results of this preliminary report showed a broad genomic heterogeneity among the studied samples; 58% of the patients were hyperdiploid and 33% displayed a chromosome 9p deletion of variable length affecting genes CDKN2A/B, two patients displayed genomic instability with a high number of focal CNAs, three patients presented unique duplications affecting 2q, 12p and 1q, respectively, and one patient displayed no copy number imbalances. The copy-number profile of 44 genes previously related to B-ALL was heterogeneous as well. Overall results highlight the need for a detailed description of the genetic alterations in ALL cancer cells in order to understand the molecular pathogenesis of the disease and to identify any prognostic markers with clinical significance.

Keywords: Acute lymphoblastic leukemia; Copy number alterations; Copy number imbalance; Molecular cytogenetics; genomic instability.