Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array
Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array
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DOI：
10.1038/sj.onc.1210330
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发表时间：
2007-08-09
期刊：
影响因子：
8
通讯作者：
Hamakawa, H.
中科院分区：
文献类型：
--
作者：
Nakaya, K.;Yamagata, H. D.;Hamakawa, H.
纯合缺失（HD）为识别候选肿瘤抑制基因的位置提供了重要资源。为了鉴定口腔癌中的抑癌基因，我们采用高分辨率比较基因组杂交（CGH）-阵列分析。我们从一个原发性口腔癌的全基因组拷贝数改变筛查中发现了一个FAT（4 q35）的纯合缺失，该基因是人类钙粘蛋白超家族的新成员。用13个口腔癌细胞系和20个原发性口腔癌细胞系的基因组聚合酶链反应和细胞系的Southern印迹法对这一结果进行了评价。我们在细胞系（3/13，23%）和原发性口腔癌（16/20，80%）中发现了频繁的FAT外显子HD。在这些细胞系中不存在FAT表达。在外显子1（9/20，45%）和外显子4（7/20，35%）中观察到纯合缺失热点。此外，在其他类型的鳞状细胞癌中也发现了基因表达的缺失。鳞状细胞癌中FAT CpG岛的甲基化状态与其表达呈负相关。我们的研究结果确定了脂肪的突变是口腔癌发展的一个重要因素，并表明脂肪的功能在一些鳞状细胞癌的重要性。
Homozygous deletions (HD) provide an important resource for identifying the location of candidate tumor suppressor genes. To identify the tumor suppressor gene in oral cancer, we employed high-resolution comparative genomic hybridization (CGH)-array analysis. We identified a homozygous loss of FAT ( 4q35), a new member of the human cadherin superfamily, from genome-wide screening of copy number alterations in one primary oral cancer. This result was evaluated by genomic polymerase chain reaction in 13 oral cancer cell lines and 20 primary oral cancers and Southern blot in the cell lines. We found frequent exonic HD of FAT in the cell lines (3/13, 23%) and in primary oral cancers (16/20, 80%). FAT expression was absent in these cell lines. Homozygous deletion hot spots were observed in exon 1 (9/20, 45%) and exon 4 (7/20, 35%). Moreover, loss of gene expression was identified in other types of squamous cell carcinoma. The methylation status of the FAT CpG island in squamous cell carcinomas correlated negatively with its expression. Our results identify mutations in FAT as an important factor in the development of oral cancer and indicate the importance of FATs function in some squamous cell carcinomas.