NEW YORK (Reuters Health) - The myelin-related gene epithelial membrane protein 3 (EMP3) is likely to be the long-sought tumor suppressor gene located on chromosome 19 in gliomas and neuroblastomas, according to a report in the April 1st issue of Cancer Research.
Moreover, senior investigator, Dr. Manel Esteller told Reuters Health, “inactivation of tumor suppressor genes by methylation is an important event for the development of cancer and, most important, can be used in the near future as a target for cancer treatments using DNA demethylation agents.”
Common genomic deletions in the 19q13 chromosomal region in gliomas and neuroblastomas suggest the presence of a tumor suppressor gene for these cancers, the authors explain, but previous efforts have failed to identify such a gene.
Dr. Esteller from the Spanish National Cancer Center, Madrid and colleagues used microarray analysis to compare the expression profile of neuroblastoma tumors and benign ganglioneuromas in an effort to identify a tumor suppressor gene for gliomas and neuroblastomas.
Though 6 underexpressed genes were identified at this locus (19q13), the authors report, only EMP3 was both downregulated 3-fold and contained a CpG island susceptible to hypermethylation.
Additional experiments confirmed the presence of EMP3 CpG island promoter hypermethylation in neuroblastoma and glioma cell lines and the association between hypermethylation and gene silencing.
Treatment of such cell lines with a demethylating drug restored their expression of EMP3 RNA transcript, the researchers note, and reintroduction of EMP3 into deficient neuroblastoma cell lines resulted in tumor suppressor-like properties.
Moreover, the researchers found that in neuroblastoma patients, EMP3 promoter-associated CpG island hypermethylation was associated with significantly higher mortality.
“Until now there were no good markers able to predict the outcome of neuroblastoma patients after the first two years,” Dr. Esteller said. “EMP3 methylation is able to do it. This can predict those patients that require a more careful and longer follow-up.”
Source: Cancer Res 2005;65:2565-2571. [ Google search on this article ]
MeSH Headings:Alkylation: Biological Sciences: Biology: Chemistry: Chemistry, Organic: Genetics: Genetics, Biochemical: Glioma: Methylation: Molecular Biology: Neoplasms: Neoplasms by Histologic Type: Neoplasms, Germ Cell and Embryonal: Neoplasms, Glandular and Epithelial: Neoplasms, Nerve Tissue: Physical Sciences: Neuroectodermal Tumors: Neoplasms, Neuroepithelial: CpG Islands: DNA Methylation: GC Rich Sequence: Biological Sciences: Diseases: Physical SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
