[DNA methylation and histone modification relate to RASSF1A gene deletion in laryngeal carcinoma tissues]

Jing Yang, Wen-yue Ji, Ya-rong Qu, Li-xia He, Xu-dong Zhao, Ming-zhu Jin
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2011, 46 (4): 308-12

OBJECTIVE: To investigate the relationship between RASSF1A gene expression and DNA methylation or histone modification in laryngeal carcinoma tissues.

METHODS: Chromatin immunoprecipitation (ChIP), methylation specific polymerase chain reaction (MSP) and realtime quantitative reverse transcription polymerase chain reaction (realtime RT-PCR) were used to analyze RASSF1A gene promoter region histone H3 lysine 9 methylation, H3 lysine 4 methylation, H3 lysine 9 acetylation, DNA methylation, and RASSF1A gene expression in laryngeal carcinoma tissue of 50 cases.

RESULTS: DNA methylation rate of gene RASSF1A was 62% in 50 cases of laryngeal carcinoma, but no DNA methylation was found in normal control group, with a significant difference (χ(2) = 15.381, P < 0.05). DNA methylation had no correlation with age, gender, differentiation degree, T stage, pathological type and lymph node metastasis (P > 0.05). The affection of DNA methylation group was more than unmethylation group to expression of gene RASSF1A (t = -3.108, P < 0.01). There was positive correlation between RASSF1A deletion and gene hypermethylation or between H3 lysine 9 methylation of RASSF1A gene promoter and DNA methylation in laryngeal carcinoma tissue(r = 0.816, P < 0.05), but there was negative correlation between H3 lysine 4 methylation of RASSF1A gene promoter and DNA methylation (r = -0.837, P < 0.05) and no correlation between H3 lysine 9 acetylation and DNA methylation (r = -0.383, P > 0.05).

CONCLUSIONS: Laryngeal tumor suppressor gene RASSF1A promoter methylation is a key factor down-regulating the gene expression, and histone modifications also plays an important role in tumor development.

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