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.
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.
Authors: Padmaja Gade; Amy S Kimball; Angela C DiNardo; Priyamvada Gangwal; Douglas D Ross; H Scott Boswell; Susan K Keay; Dhananjaya V Kalvakolanu Journal: J Biol Chem Date: 2016-09-02 Impact factor: 5.157
Authors: Brandon J Metge; Andra R Frost; Judy A King; Donna Lynn Dyess; Danny R Welch; Rajeev S Samant; Lalita A Shevde Journal: Clin Exp Metastasis Date: 2008-06-20 Impact factor: 5.150
Authors: Nancy Dumont; Yongping G Crawford; Mahvash Sigaroudinia; Shefali S Nagrani; Matthew B Wilson; Gertrude C Buehring; Gulisa Turashvili; Samuel Aparicio; Mona L Gauthier; Colleen A Fordyce; Kimberly M McDermott; Thea D Tlsty Journal: Breast Cancer Res Date: 2009-12-08 Impact factor: 6.466
Authors: Kyung-Ok Uhm; Jung Ok Lee; Yun Mi Lee; Eun Soo Lee; Hyeon Soo Kim; Sun-Hwa Park Journal: J Cancer Res Clin Oncol Date: 2009-08-05 Impact factor: 4.553
Authors: Christina Piperi; Marios S Themistocleous; George A Papavassiliou; Elena Farmaki; Georgia Levidou; Penelope Korkolopoulou; Christos Adamopoulos; Athanasios G Papavassiliou Journal: Mol Med Date: 2009-10-12 Impact factor: 6.354