Hypermethylation of the RASSF1A gene in gliomas
- PMID: 15469871
- DOI: 10.1016/j.cccn.2004.07.006
Hypermethylation of the RASSF1A gene in gliomas
Abstract
Background: Promoter methylation is an important pathway in transcriptional silencing of tumor suppressor genes (TSGs) in brain tumors. The identified 3p21.3 tumor suppressor gene RAS association domain family protein 1A (RASSF1A) is highly methylated in primary lung, breast and other tumors. We investigated the promoter methylation and gene expression of RASSF1A in gliomas.
Methods: The methylation status of the promoter region of RASSF1A, p16INK4A and death-associated protein kinase (DAPK) genes was analyzed by methylation-specific PCR (MSP) in 41 surgically resected gliomas. RASSF1A expression was also detected by reverse-transcription polymerase chain reaction (RT-PCR) in 28 glioma tissues.
Results: The frequencies of RASSF1A, p16INK4A and DAPK promoter methylation were 13/41 (31.7%), 3/41 (7.3%) and 6/41 (14.6%) respectively. However, the methylations of those genes were not correlated with the clinical characteristics of patients (tumor grade, tumor types and sex). Among 28 glioma tissues, 6 showed the loss of the gene (21.4%). Promoter hypermethylation of RASSF1A is associated with loss of gene expression in glioma tissues. (p=0.022).
Conclusions: Our results suggested that the RASSF1A gene might play an important role in glioma carcinogenesis. It also gives us an insight for future glioma medical therapy with a demethylating agent.
Similar articles
-
Promoter methylation of p16INK4a, RASSF1A, and DAPK is frequent in salivary adenoid cystic carcinoma.Cancer. 2005 Aug 15;104(4):771-6. doi: 10.1002/cncr.21215. Cancer. 2005. PMID: 15959912
-
Frequent epigenetic inactivation of RASSF1A and BLU genes located within the critical 3p21.3 region in gliomas.Oncogene. 2004 Mar 25;23(13):2408-19. doi: 10.1038/sj.onc.1207407. Oncogene. 2004. PMID: 14743209
-
Promoter hypermethylation of multiple genes in early gastric adenocarcinoma and precancerous lesions.Hum Pathol. 2009 Nov;40(11):1534-42. doi: 10.1016/j.humpath.2009.01.029. Epub 2009 Aug 19. Hum Pathol. 2009. PMID: 19695681
-
Methylation of the RASSF1A gene in human cancers.Biol Chem. 2002 Jun;383(6):907-14. doi: 10.1515/BC.2002.097. Biol Chem. 2002. PMID: 12222680 Review.
-
[p16 tumor suppressor gene alteration in brain tumors].No To Shinkei. 1998 Jun;50(6):511-7. No To Shinkei. 1998. PMID: 9656246 Review. Japanese. No abstract available.
Cited by
-
RASSF1A, BLU, NORE1A, PTEN and MGMT expression and promoter methylation in gliomas and glioma cell lines and evidence of deregulated expression of de novo DNMTs.Brain Pathol. 2009 Apr;19(2):279-92. doi: 10.1111/j.1750-3639.2008.00185.x. Epub 2008 Jun 25. Brain Pathol. 2009. PMID: 18616639 Free PMC article.
-
Human mammary cancer progression model recapitulates methylation events associated with breast premalignancy.Breast Cancer Res. 2009;11(6):R87. doi: 10.1186/bcr2457. Epub 2009 Dec 8. Breast Cancer Res. 2009. PMID: 19995452 Free PMC article.
-
Aberrant DNA methylation of integrin α4 in human breast cancer.Tumour Biol. 2014 Jul;35(7):7079-84. doi: 10.1007/s13277-014-1952-7. Epub 2014 Apr 24. Tumour Biol. 2014. PMID: 24756760
-
Potential Epigenetic-Based Therapeutic Targets for Glioma.Front Mol Neurosci. 2018 Nov 15;11:408. doi: 10.3389/fnmol.2018.00408. eCollection 2018. Front Mol Neurosci. 2018. PMID: 30498431 Free PMC article. Review.
-
Death-associated Protein Kinase-1 Expression and Autophagy in Chronic Lymphocytic Leukemia Are Dependent on Activating Transcription Factor-6 and CCAAT/Enhancer-binding Protein-β.J Biol Chem. 2016 Oct 14;291(42):22030-22042. doi: 10.1074/jbc.M116.725796. Epub 2016 Sep 2. J Biol Chem. 2016. PMID: 27590344 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
