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Inactivation patterns of NF2 and DAL-1/4.1B (EPB41L3) in sporadic meningioma

Fabio Nunes1, Yiping Shen, Yo Niida

  • 1Department of Neurology, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA. fnunes@partners.org

Cancer Genetics and Cytogenetics
|October 11, 2005
PubMed

Insights

The DAL-1/4.1B gene is less frequently involved in sporadic meningiomas than previously thought. Loss of heterozygosity at the DAL-1/4.1B locus suggests a role in tumor progression, not initiation.

Area of Science:

  • Neuro-oncology
  • Cancer Genetics
  • Molecular Biology

Background:

  • The molecular mechanisms driving meningioma development and progression are not fully elucidated.
  • While the neurofibromatosis 2 (NF2) gene is frequently inactivated in meningiomas, the genetic alterations in tumors without NF2 inactivation remain unclear.
  • Conflicting data exists regarding the role of the DAL-1/4.1B tumor suppressor gene in meningioma pathogenesis.

Purpose of the Study:

  • To investigate the frequency and mechanisms of loss of heterozygosity (LOH) at the NF2 and DAL-1/4.1B loci in sporadic meningiomas.
  • To determine the role of the DAL-1/4.1B locus in meningioma initiation versus progression.
  • To identify copy number alterations in sporadic meningiomas using array comparative genomic hybridization.

Main Methods:

  • Microsatellite marker analysis of 63 sporadic meningiomas to assess LOH at NF2 and DAL-1/4.1B loci.
  • Array comparative genomic hybridization (aCGH) analysis of 52 tumors to detect copy number changes on chromosomes 18 and 22.
  • Correlation of LOH status with tumor characteristics and copy number alterations.

Main Results:

  • LOH at the NF2 locus was observed in 66% of informative tumors, while LOH at the DAL-1/4.1B locus occurred in 19%.
  • The majority (92%) of tumors with DAL-1/4.1B LOH also exhibited NF2 LOH.
  • Monosomy or large deletions of chromosomes 18 and 22 were the primary mechanisms underlying LOH at these loci.
  • Most meningiomas showed monosomy rather than isodisomy at the NF2 and DAL-1/4.1B loci.

Conclusions:

  • The DAL-1/4.1B locus is implicated less frequently in sporadic meningiomas than previously reported.
  • Evidence suggests DAL-1/4.1B acts as a tumor progression locus rather than an initiation locus.
  • Monosomy is the predominant mechanism for LOH at the NF2 and DAL-1/4.1B loci in sporadic meningiomas.

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