Loss of heterozygosity of TRIM3 in malignant gliomas

Jean-Louis Boulay1, Urs Stiefel, Elisabeth Taylor

  • 1Department of Biomedicine, University Hospital, Basel, Switzerland. Jean-Louis.Boulay@unibas.ch

BMC Cancer
|March 3, 2009
PubMed
Abstract

Insights

Loss of heterozygosity (LOH) in chromosome 11p15.5 suggests the Tripartite motif protein 3 (TRIM3) gene may act as a brain tumor suppressor. This finding could lead to new diagnostic targets for malignant gliomas.

Area of Science:

  • Neuro-oncology
  • Cancer Genomics
  • Molecular Biology

Background:

  • Malignant gliomas are aggressive brain tumors with poor prognosis and limited treatment efficacy.
  • Glioma invasiveness complicates surgical resection and necessitates novel therapeutic targets.
  • Human Tripartite motif protein 3 (TRIM3) is a homolog of Drosophila brain tumor (brat) and may function as a tumor suppressor.

Purpose of the Study:

  • To investigate the role of TRIM3 in malignant glioma development.
  • To identify potential tumor suppressor genes within the 11p15.5 chromosomal region.

Main Methods:

  • Analysis of 70 primary human gliomas of all grades.
  • Somatic deletion mapping and single nucleotide polymorphism analysis of chromosome segment 11p15.5.
  • Quantitative real-time PCR to assess TRIM3 gene dosage.

Main Results:

  • Loss of heterozygosity (LOH) at 11p15.5 was identified in 24% of gliomas.
  • A common 130 kb minimal region of loss within the TRIM3 locus was defined.
  • Homozygous deletions of TRIM3 were detected in two glioma cases with LOH.

Conclusions:

  • Loss of heterozygosity in chromosome segment 11p15.5 suggests TRIM3 is a candidate brain tumor suppressor gene.
  • TRIM3 alterations may contribute to malignant glioma pathogenesis.