Loss of protein expression and recurrent DNA hypermethylation of the GNG7 gene in squamous cell carcinoma of the head and neck.

Loss of protein expression and recurrent DNA hypermethylation of the GNG7 gene in squamous cell carcinoma of the head and neck.
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DOI:
10.1007/s13353-011-0079-4
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发表时间:
2012-05
影响因子:
2.4
通讯作者:
Giefing, Maciej
Giefing, Maciej
中科院分区:
生物学3区
文献类型:
--
作者:
Hartmann, Sylvia;Szaumkessel, Marcin;Salaverria, Itziar;Simon, Ronald;Sauter, Guido;Kiwerska, Katarzyna;Gawecki, Wojciech;Bodnar, Magdalena;Marszalek, Andrzej;Richter, Julia;Brauze, Damian;Zemke, Natalia;Jarmuz, Malgorzata;Hansmann, Martin-Leo;Siebert, Reiner;Szyfter, Krzysztof;Giefing, Maciej

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虽然GNG7在癌症中的下调已经被报道过,但它在癌症发生中的作用却知之甚少。它属于一个大的G蛋白家族,可能参与细胞接触诱导的生长停滞和肿瘤抑制功能。在本研究中,我们用免疫组织化学方法对188例喉部或口底肿瘤进行了GNG7蛋白染色,并与临床病理资料进行对照。此外,我们还进行了亚硫酸氢盐焦磷酸测序,以分析GNG7启动子的甲基化。我们发现68例(36%)GNG7蛋白表达反复丢失,(42/98;43%)原发肿瘤以年轻患者为主(p < 0.001)。GNG7表达缺失与GNG7启动子区域高甲基化相关(p < 0.001)。此外,GNG7蛋白表达缺失与肿瘤大小(p = 0.012)和无颈部转移(p = 0.02)相关,而持续表达与角化(p = 0.008)相关。综上所述,GNG7蛋白表达缺失是头颈癌的常见事件。此外,我们的数据表明GNG7启动子区域的高甲基化可能是观察到的失活的机制。
Although down-regulation of GNG7 in cancer was reported before, its role in carcinogenesis is poorly understood. It belongs to a family of large G-proteins that may be involved in cell-contact-induced growth arrest and function in tumor suppression. In the present study, we stained immunohistochemically 188 tumors derived from larynx or floor of the mouth for GNG7 protein and confronted it with clinicopathologic data. Moreover, we performed bisulfite pyrosequencing to analyze GNG7 promoter methylation. We identified recurrent loss of GNG7 protein expression in 68/188 (36%) cases and promoter hypermethylation in (42/98; 43%) primary tumors, predominantly in young patients (p < 0.001). Loss of GNG7 expression correlated with hypermethylation of GNG7 promoter region (p < 0.001). Moreover, loss of GNG7 protein expression correlated with tumor size (p = 0.012) and lack of cervical metastasis (p = 0.02) whereas sustained expression correlated with keratinization (p = 0.008). Taken together, loss of GNG7 protein expression is a frequent event in head and neck cancer. Moreover, our data suggest that hypermethylation of the promoter region of GNG7 is probably the mechanism of the observed inactivation.
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