Concurrent hypermethylation of multiple genes is associated with grade of oligodendroglial tumors
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AbstractCurrent evidence suggests that epigenetic changes play an important role in the evolution of human cancers. In this study, we evaluated whether hypermethylation of CpG islands at the gene promotor regions of several tumor-related genes is involved in the carcinogenesis of oligodendroglial tumors. We examined the methylation status of I I genes in a series of 43 oligodendroglial tumors (19 oligodendrogliomas, 13 anaplastic oligodendrogliomas, 9 oligoastrocytomas, and 2 anaplastic oligoastrocytomas) by methylation-specific polymerase chain reaction. Our results showed that hypermethylation of CpG islands was detectable in 8 of I I genes studied and 74% of tumors were hypermethylated in at least I gene. Promotor hypermethylations were detected in O-6-methylguanine-DNA methyltransferase (MGMT), RB1. estrogen receptor, p73, p16(INK4a), death-associated protein kinase. p15(INK4b), and p14(ARF) at 60%, 34%, 30%. 16%, 12%, 10%, 7%, and 2%, respectively. No hypermethylation was detected in the promotors of glutathione-S-transferase P1, von Hippel-Lindau or the DIVA mismatch repair (hMLH1) genes. Statistical analysis revealed that concordant hypermethylation of at least 2 genes, p16(INKL4a) and p15(INK4b) were significantly associated with anaplastic oligodendroglial tumors, and hypermethylation of MGMT was significantly associated with loss of chromosome 19q and with combined loss of chromosomes 1p and 19q. More importantly, several candidate tumor suppressor genes such as p16(INK4a) p15(INK4b), and p73 that were previously reported as unmutated in oligodendroglial tumors were found to be hypermethylated in their CpG islands. Taken together, we conclude that hypermethylation of CpG islands is a common epigenetic event that is associated with the development of oligodendroglial tumors.
All Author(s) ListDong SM, Pang JCS, Poon WS, Hu J, To KF, Chang AR, Ng HK
Journal nameJournal of Neuropathology and Experimental Neurology
Volume Number60
Issue Number8
Pages808 - 816
LanguagesEnglish-United Kingdom
KeywordsCpG islands; methylation; O-6-methylguanine-DNA methyltransferase; oligoastrocytoma; oligodendroglioma; p73
Web of Science Subject CategoriesClinical Neurology; CLINICAL NEUROLOGY; Neurosciences; NEUROSCIENCES; Neurosciences & Neurology; Pathology; PATHOLOGY

Last updated on 2020-07-07 at 02:42