Yanaihara N, Kohno T, Takakura S, Takei K, Otsuka A, Sunaga N, Takahashi M, Yamazaki M, Tashiro H, Fukuzumi Y, Fujimori Y, Hagiwara K, Tanaka T, Yokota J
Biology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan.
Genomics. 2001 Mar 1;72(2):169-79. doi: 10.1006/geno.2000.6454.
Here, we report the complete genomic sequence and the characterization of the 311-kb region of 18q21, a candidate tumor suppressor locus containing a region of homozygous deletion in a lung cancer cell line, Ma29. This region contained two known genes, SMAD4 and ME2 (mitochondrial malate oxydoreductase), and two novel genes, D29 (deleted in Ma29 HGMW-approved symbol ELAC1), encoding an evolutionarily conserved protein, and B29 (beside the Ma29 deletion HGMW-approved symbol C18orf3), with no significant homology to any known genes. The deleted DNA segment in Ma29, which was estimated to be 195 kb in size, included all the coding exons of ME2 and D29, but not the coding exons of SMAD4 and B29. The deleted region also included exon 0, a 5'-noncoding exon, of SMAD4, and the expression of SMAD4 was greatly reduced in Ma29 cells. Mutations of SMAD4 and D29 were detected in 1 of 45 lung cancer cell lines examined, while those of ME2 and B29 were not detected, indicating that these four genes are not major targets for 18q21 deletions. The physical and transcriptional map constructed in this study will provide basic information for the identification of a tumor suppressor gene(s) at 18q21 involved in lung carcinogenesis.
在此，我们报告了18q21区域311kb的完整基因组序列及其特征，该区域是一个候选肿瘤抑制基因座，在肺癌细胞系Ma29中存在纯合缺失区域。该区域包含两个已知基因SMAD4和ME2（线粒体苹果酸氧化还原酶），以及两个新基因，D29（在Ma29中缺失，HGMW批准符号为ELAC1），编码一种进化上保守的蛋白质，和B29（在Ma29缺失旁，HGMW批准符号为C18orf3），与任何已知基因均无明显同源性。Ma29中估计大小为195kb的缺失DNA片段包含ME2和D29的所有编码外显子，但不包含SMAD4和B29的编码外显子。缺失区域还包括SMAD4的外显子0，一个5'非编码外显子，并且SMAD4在Ma29细胞中的表达大大降低。在所检测的45个肺癌细胞系中，在1个细胞系中检测到SMAD4和D29的突变，而未检测到ME2和B29的突变，这表明这四个基因不是18q21缺失的主要靶点。本研究构建的物理和转录图谱将为鉴定参与肺癌发生的18q21肿瘤抑制基因提供基础信息。
