Mutation analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human colon cancer using genomic DNA and Intron primers
Mutation analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human colon cancer using genomic DNA and Intron primers
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DOI：
10.1038/sj.onc.1200938
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发表时间：
1997-03-13
期刊：
影响因子：
8
通讯作者：
Harris, CC
中科院分区：
文献类型：
--
作者：
Takenoshita, S;Tani, M;Harris, CC
在几种表现出微卫星不稳定性的人类癌症中已检测到转化生长因子 β II 型受体 (TGF β RII) 基因的突变。为了扩展对该基因的分析，我们之前研究了 TGF beta RII 的外显子-内含子组织。基因并定义了七个外显子和侧翼内含子序列。在这项研究中，我们进一步确定了这七个外显子周围的核苷酸序列，并设计了八组基于内含子的引物来检查TGFβRII基因的整个编码区。使用这些引物，我们筛选了 30 种散发性结直肠癌的基因组 DNA 序列中的 TGF beta RII 突变。基因。在 30 个肿瘤中的两个中检测到 TGF beta RII 突变，并且均表现出微卫星不稳定性。一个在外显子3的聚腺嘌呤束中存在缺失，另一个在位于外显子7的激酶结构域中存在点突变。在外显子1、2、4、5和6中没有突变。这些结果进一步暗示聚腺嘌呤束和激酶结构域是具有基因组不稳定性的细胞中TGFβRII基因的突变热点，并表明在缺乏基因组不稳定性的细胞中TGFβRII基因突变很少发生。
Mutations in the transforming growth factor beta type II receptor (TGF beta RII) gene have been detected in several human cancers exhibiting microsatellite instability. To extend analyses of this gene, we previously investigated the exon-intron organization of the TGF beta RII. gene and defined seven exons and flanking intron sequences. In this study, we further determined the nucleotide sequences surrounding these seven exons and designed eight sets of intron-based primers to examine the entire coding region of the TGF beta RII gene. Using these primers, we screened genomic DNA sequences from 30 sporadic colorectal cancers for mutations of the TGF beta RII. gene. TGF beta RII mutations were detected in two of 30 tumors and both displayed microsatellite instability. One had a deletion in a polyadenine tract in exon 3 and the other had a point mutation in the kinase domain located in exon 7. There were no mutations in exons 1, 2, 4, 5 and 6. These results further implicate the polyadenine tract and kinase domain as mutational hotspots in the TGF beta RII gene in cells,vith genomic instability and suggest that TGF beta RII gene mutations occur rarely in cells lacking genomic instability.