Mutations of the E2F4 gene in hematological malignancies having microsatellite instability

Blood. 2000 Feb 15;95(4):1509-10.

Abstract

Mutations of coding repeats within the E2F4, TGF-betaRII, BAX, IGFIIR, and hMSH3 are critical targets of microsatellite instability (MSI) in many kinds of cancers. We analyzed 9 childhood acute lymphoblastic leukemia (ALL) samples, 5 acute myelocytic leukemia (AML) samples, and 10 adult T-cell leukemia (ATL) samples having MSI to determine whether they had mutations of the E2F4, TGF-betaRII, BAX, IGFIIR, and hMSH3 genes. Frameshift mutations were found at trinucleotide repeats within a coding exon of the E2F4 gene in 2 of 10 (20%) ATL samples and 1 of 9 (11%) childhood ALL samples. No mutations were found in the TGF-betaRII, BAX, IGFIIR, and hMSH3 genes. E2F4 is a transcription factor that influences the cell-cycle progression. These results suggest that mutations of the E2F4 gene, presumably caused by an abnormality of one of the DNA repair genes, may play an important role in development of ATL and childhood ALL. (Blood. 2000;95:1509-1510)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Child
  • DNA-Binding Proteins / genetics*
  • E2F4 Transcription Factor
  • Exons
  • Hematologic Neoplasms / genetics*
  • Humans
  • Leukemia / genetics*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia-Lymphoma, Adult T-Cell / genetics
  • Microsatellite Repeats*
  • Multidrug Resistance-Associated Proteins*
  • MutS Homolog 3 Protein
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2*
  • Receptor, IGF Type 2 / genetics
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Transcription Factors / genetics*
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • DNA-Binding Proteins
  • E2F4 Transcription Factor
  • MSH3 protein, human
  • Multidrug Resistance-Associated Proteins
  • MutS Homolog 3 Protein
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor, IGF Type 2
  • Receptors, Transforming Growth Factor beta
  • Transcription Factors
  • bcl-2-Associated X Protein
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • multidrug resistance-associated protein 1