Identification and Characterization of Novel Fusion Genes with Potential Clinical Applications in Mexican Children with Acute Lymphoblastic Leukemia

Int J Mol Sci. 2019 May 15;20(10):2394. doi: 10.3390/ijms20102394.

Abstract

Acute lymphoblastic leukemia is the most common type of childhood cancer worldwide. Mexico City has one of the highest incidences and mortality rates of this cancer. It has previously been recognized that chromosomal translocations are important in cancer etiology. Specific fusion genes have been considered as important treatment targets in childhood acute lymphoblastic leukemia (ALL). The present research aimed at the identification and characterization of novel fusion genes with potential clinical implications in Mexican children with acute lymphoblastic leukemia. The RNA-sequencing approach was used. Four fusion genes not previously reported were identified: CREBBP-SRGAP2B, DNAH14-IKZF1, ETV6-SNUPN, ETV6-NUFIP1. Although a fusion gene is not sufficient to cause leukemia, it could be involved in the pathogenesis of the disease. Notably, these new translocations were found in genes encoding for hematopoietic transcription factors which are known to play an important role in leukemogenesis and disease prognosis such as IKZF1, CREBBP, and ETV6. In addition, they may have an impact on the prognosis of Mexican pediatric patients with ALL, with the potential to be included in the current risk stratification schemes or used as therapeutic targets.

Keywords: RNA sequencing; chromosomal translocation; fusion gene; genetic variations; leukemogenesis; risk stratification.

MeSH terms

  • Adolescent
  • Adult
  • CREB-Binding Protein / genetics
  • Child
  • Child, Preschool
  • Dyneins / genetics
  • ETS Translocation Variant 6 Protein
  • Female
  • GTPase-Activating Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Rearrangement
  • Humans
  • Ikaros Transcription Factor / genetics
  • Infant
  • Male
  • Mexico
  • Nuclear Proteins / genetics
  • Oncogene Proteins, Fusion / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • Proto-Oncogene Proteins c-ets / genetics
  • RNA Cap-Binding Proteins / genetics
  • RNA-Binding Proteins / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Repressor Proteins / genetics
  • Translocation, Genetic / genetics*
  • Young Adult

Substances

  • GTPase-Activating Proteins
  • IKZF1 protein, human
  • NUFIP1 protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-ets
  • RNA Cap-Binding Proteins
  • RNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • SNUPN protein, human
  • SRGAP3 protein, human
  • Ikaros Transcription Factor
  • CREB-Binding Protein
  • CREBBP protein, human
  • DNAH14 protein, human
  • Dyneins