Somatic deletion mapping on chromosome 10 and sequence analysis of PTEN/MMAC1 point to the 10q25-26 region as the primary target in low-grade and high-grade gliomas

Oncogene. 1998 Jun 25;16(25):3331-5. doi: 10.1038/sj.onc.1201832.

Abstract

The 10q25-26 region between the dinucleotide markers D10S587 and D10S216 is deleted in glioblastomas and, as we have recently shown, in low-grade oligodendrogliomas. We further refined somatic mapping on 10q23-tel and simultaneously assessed the role of the candidate tumor suppressor gene PTEN/MMAC1 in glial neoplasms by sequence analysis of eight low-grade and 24 high-grade gliomas. These tumors were selected for partial or complete loss of chromosome 10 based on deletion mapping with increased microsatellite marker density at 10q23-tel. Three out of eight (38%) low-grade and 3/24 (13%) high-grade gliomas exclusively target 10q25-26. We did not find a tumor only targeting 10q23.3, and most tumors (23/32, 72%) showed large deletions on 10q including both regions. The sequence analysis of PTEN/MMAC1 revealed nucleotide alterations in 1/8 (12.5%) low-grade gliomas in a tumor with LOH at l0q21-qtel and in 5/21 (24%) high-grade gliomas displaying LOH that always included 10q23-26. Our refined mapping data point to the 10q25-26 region as the primary target on 10q, an area that also harbors the DMBT1 candidate tumor suppressor gene. The fact that we find hemizygous deletions at 10q25-qtel in low-grade astrocytomas and oligodendrogliomas - two histologically distinct entities of gliomas - suggests the existence of a putative suppressor gene involved early in glial tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10 / genetics*
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • Dinucleotide Repeats / genetics
  • Gene Deletion
  • Genes, Tumor Suppressor / genetics
  • Genetic Markers / genetics
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Loss of Heterozygosity
  • Mutation / genetics
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases*
  • Protein Tyrosine Phosphatases / genetics*
  • Sequence Analysis, DNA
  • Severity of Illness Index
  • Tumor Suppressor Proteins*

Substances

  • DNA, Neoplasm
  • Genetic Markers
  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • Protein Tyrosine Phosphatases
  • PTEN Phosphohydrolase
  • PTEN protein, human