Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas

David H. Gutmann, Jessica Donahoe, Arie Perry, Nancy Lemke, Karen Gorse, Kanokwan Kittiniyom, Sandra A. Rempel, Jorge A. Gutierrez, Irene F. Newsham

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

Meningiomas are common nervous system tumors, whose molecular pathogenesis is poorly understood. To date, the most frequent genetic alteration detected in these tumors is loss of heterozygosity (LOH) on chromosome 22q. This finding led to the identification of the neurofibromatosis 2 (NF2) tumor suppressor gene on 22q12, which is inactivated in 40% of sporadic meningiomas. The NF2 gene product, merlin (or schwannomin), is a member of the protein 4.1 family of membrane-associated proteins, which also includes ezrin, radixin and moesin. Recently, we identified another protein 4.1 gene, DAL-1 (differentially expressed in adenocarcinoma of the lung) located on chromosome 18p11.3, which is lost in ~ 60% of non-small cell lung carcinomas, and exhibits growth-suppressing properties in lung cancer cell lines. Given the homology between DAL-1 and NF2 and the identification of significant LOH in the region of DAL-1 in lung, breast and brain tumors, we investigated the possibility that loss of expression of DAL-1 was important for meningioma development. In this report, we demonstrate DAL-1 loss in 60% of sporadic meningiomas using LOH, RT-PCR, western blot and immunohistochemistry analyses. Analogous to merlin, we show that DAL-1 loss is an early event in meningioma tumorigenesis, suggesting that these two protein 4.1 family members are critical growth regulators in the pathogenesis of meningiomas. Furthermore, our work supports the emerging notion that membrane-associated alterations are important in the early stages of neoplastic transformation and the study of such alterations may elucidate the mechanism of tumorigenesis shared by other tumor types.

Original languageEnglish (US)
Pages (from-to)1495-1500
Number of pages6
JournalHuman molecular genetics
Volume9
Issue number10
DOIs
StatePublished - Jun 12 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Gutmann, D. H., Donahoe, J., Perry, A., Lemke, N., Gorse, K., Kittiniyom, K., Rempel, S. A., Gutierrez, J. A., & Newsham, I. F. (2000). Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas. Human molecular genetics, 9(10), 1495-1500. https://doi.org/10.1093/hmg/9.10.1495