Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas
Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas
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DOI：
10.1016/j.gene.2005.02.014
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发表时间：
2005-08-15
期刊：
影响因子：
3.5
通讯作者：
Nagai, N
中科院分区：
文献类型：
--
作者：
Gunduz, M;Nagatsuka, H;Nagai, N
我们之前展示了ING家族的两个成员，ING1和ING3，作为头颈癌的肿瘤抑制基因。人类基因组测序的进展为ING家族基因的新成员提供了额外的信息。ING4定位于染色体12p13.31区域，含有与ING家族蛋白高度同源的PHD结构域。我们用6个高度多态的微卫星标记分析了50例头颈部鳞状细胞癌12p12-13区域的杂合性缺失，发现66%(33/50)的病例存在等位基因缺失。为了阐明ING4在头颈部癌症发生中的作用，我们首先检查了肿瘤样本中的突变状态。由于在头颈部肿瘤中未发现ING4基因突变，我们检测了该基因的mRNA表达水平。实时荧光定量RT-PCR分析显示，与匹配的正常组织相比，76%的原发肿瘤组织中ING4基因的表达水平降低。由于已经显示了ING家族其他成员的P53依赖通路，我们检测了P53突变状态，并与肿瘤标本中ING4mRNA的表达进行了比较。然而，还没有检测到这种直接关系。综上所述，ING4基因的频繁缺失和表达下降提示它是一个二级抑癌基因，可能在头颈癌中起重要作用。(C)2005 Elsevier B.V.保留所有权利。
We previously showed two members of the ING family, ING1 and ING3 as a tumor suppressor gene in head and neck cancer. Progress in human genome sequencing provided additional information of the new members of the ING family genes. ING4 is localized to chromosome 12p13.31 region and harbors the PHD domain highly homologous among ING family proteins. We analyzed loss of heterozygosity at 12p12-13 region in 50 head and neck squamous cell carcinomas by using six highly polymorphic microsatellite markers and found allelic loss in 66% (33/50) of the informative cases. To clarify the role of ING4 in head and neck carcinogenesis, we first checked mutation status in tumor samples. As mutation of the ING4 gene was not found in head and neck cancers, we examined the mRNA expression level. Quantitative real-time RT-PCR analysis demonstrated decreased expression of ING4 mRNA in 76% of primary tumors as compared with that of matched normal samples. Since p53 dependent pathways of other ING family members have been shown, we examined p53 mutation status and compared with ING4 mRNA expression in tumor samples. However, no such direct relationship has been detected. In conclusion, frequent deletion and decreased mRNA expression of ING4 suggested it as a class two tumor suppressor gene and may play an important role in head and neck cancer. (c) 2005 Elsevier B.V. All rights reserved.