Related to testes-specific, vespid and pathogenesis protein-1 is regulated by methylation in glioblastoma.

Elad Jacoby,Simona Cazacu,Tamar Fisher,Sarit Eder,Zvi R Cohen,Moshe Leitner,Michal Yalon,Gideon Rechavi,Cunli Xiang,Ninette Amariglio,Amos Toren,Tom Mikkelsen,Chaya Brodie,Yehudit Cohen

doi:10.3892/ol.2014.1829

Abstract

Related to testes-specific, vespid and pathogenesis protein-1 (RTVP-1), also known as glioma pathogenesis-related protein 1, is highly expressed and has oncogenic features in glioblastoma (GBM; World Health Organization class IV). Promoter methylation has been found to control RTVP-1 expression in prostate carcinoma, Wilms’ tumor, acute myeloid leukemia and melanoma. In this bi-institutional study, the methylation status of RTVP-1 in astrocytic brain malignancies (GBM and oligodendroglioma) was examined. The RTVP-1 promoter was hypomethylated in GBM compared with non-tumor brain samples, but was hypermethylated in oligodendroglioma. RTVP-1 methylation correlated with RTVP-1 expression at the mRNA level. In GBM, hypermethylation of the RTVP-1 promoter was associated with improved overall survival although with no statistical significance.

Highlights

Glial tumors are the most common brain malignancies, accounting for major morbidity and mortality of adults and Present address: 6Bloomberg Children's Center, Room 11379, Johns Hopkins Hospital, 1800 Orleans Street, Baltimore, MD 21287, USAKey words: glioblastoma, related to testes‐specific vespid and pathogenesis protein‐1, glioma pathogenesis‐related protein 1, methylation children
RTVP‐1 is normally expressed in the heart, spleen, muscle, bone marrow, placenta, adrenal and prostate [8]
In GBM, RTVP‐1 is an overexpressed oncogene associated with increased proliferation, enhanced invasion and inhibition of apoptosis [6,7,8,9,15]

Summary

Introduction

Present address: 6Bloomberg Children's Center, Room 11379, Johns Hopkins Hospital, 1800 Orleans Street, Baltimore, MD 21287, USA. DNA methylation, one of the most common epigenetic modifications, has been widely described in cancer, which exhibits global DNA hypomethylation in addition to significant hypermethylation (and downregulation) of tumor suppressor genes [3]. Aberrant DNA methylation is well described in GBM [4,5]. Previous studies have reported that RTVP‐1 can be epigenetically regulated [10,11,12,13], but this has not been demonstrated in central nervous system tissue or tumors. RTVP‐1 promoter methylation status in GBM and the association of promoter methylation with disease progression and patient outcome were examined

Materials and methods

Results

Discussion

Esteller M

Findings

18. Thompson TC