Characterization of the human TESTIN gene localized in the FRA7G region at 7q31.2
Characterization of the human TESTIN gene localized in the FRA7G region at 7q31.2
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DOI：
10.1006/geno.2000.6272
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发表时间：
2000-08-15
期刊：
影响因子：
4.4
通讯作者：
Croce, CM
中科院分区：
文献类型：
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作者：
Tatarelli, C;Linnenbach, A;Croce, CM
癌症相关的染色体畸变通常涉及含有脆性位点的区域。FRA7G是一个常见的aphidicolin诱导的脆性位点7q31.2，在人类恶性肿瘤中表现出杂合性丢失。为了研究FRA7G的结构，我们构建了一个跨越标记D7S486和Met H之间区域的细菌人工染色体重叠群。FRA7G序列的分析使我们能够确定一个基因编码的421个氨基酸的蛋白质与三个LIM域和89%的一致性，小鼠睾丸素。我们确定了人类TESTIN基因座的基因组结构，并表征了三种替代转录本。尽管TESTIN mRNA在所有检查的正常人体组织中表达，但我们观察到在22%的癌细胞系和44%的血液恶性肿瘤细胞系中缺乏表达。我们进一步确定，在大多数这些情况下，TESTIN表达的失活是由于CpG岛的甲基化。26个肿瘤细胞系中TESTIN编码区的分析揭示了三个错义突变。我们的研究结果表明，TESTIN可能代表一个候选的肿瘤抑制基因在7q31.2。(C)北京大学出版社.
Cancer-associated chromosomal aberrations often involve regions containing fragile sites. FRA7G is a common aphidicolin-inducible fragile site at 7q31.2, showing loss of heterozygosity in human malignancies. To investigate the structure of FRA7G, we constructed a bacterial artificial chromosome contig spanning the region between marker D7S486 and Met H. Analysis of the FRA7G sequence allowed us to identify a gene encoding a 421-amino-acid protein with three LIM domains and 89% identity to murine Testin. We determined the genomic structure of the human TESTIN locus and characterized three alternative transcripts. Although TESTIN mRNA is expressed in all normal human tissues examined, we observed lack of expression in 22% of cancer cell lines and 44% of the cell lines derived from hematological malignancies. We further determined that in most of these cases the inactivation of TESTIN expression is due to methylation of a CpG island, Analysis of the TESTIN coding region in 26 tumor cell lines revealed three missense mutations. Our findings suggest that TESTIN may represent a candidate tumor suppressor gene at 7q31.2. (C) 2000 Academic Press.