Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia

Haematologica. 2010 Jan;95(1):158-62. doi: 10.3324/haematol.2009.007526. Epub 2009 Jul 7.

Abstract

Although deletions of cell cycle regulatory gene loci have long been reported in various malignancies, little is known regarding their relevance in pediatric T-cell lymphoblastic lymphoma (T-LBL) and T-cell lymphoblastic leukemia (TALL). The current study focused on loss of heterozygosity (LOH) analyses of the CDKN2A/B (chromosome 9p), ATM (chromosome 11q) and p53 (chromosome 17p) gene loci. Frequencies of LOH were compared in 113 pediatric T-LBL and 125 T-ALL who were treated uniformly according to ALL-BFM strategies. Furthermore, LOH findings were correlated with clinical characteristics and tested for their prognostic relevance. LOH at 9p was detected in 47% of T-LBL and 51% of T-ALL, and was associated with male gender in both. In T-ALL, LOH at 9p was associated with favorable initial treatment response. A tendency for favorable event-free-survival was observed in LOH 9p positive T-LBL. The frequency of LOH at chromosomes 11q and 17p was 5% or less for both diseases.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics*
  • Child
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Loci / genetics*
  • Genetic Markers / genetics
  • Humans
  • Leukemia, T-Cell / genetics*
  • Leukemia, T-Cell / mortality
  • Leukemia, T-Cell / pathology
  • Loss of Heterozygosity / genetics
  • Male
  • Microsatellite Repeats / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Protein Serine-Threonine Kinases / genetics*
  • Survival Rate / trends
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Proteins / genetics*

Substances

  • CDKN2B protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Genetic Markers
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases