Aberrant splicing of the TSG101 and FHIT genes occurs frequently in multiple malignancies and in normal tissues and mimics alterations previously described in tumours
Aberrant splicing of the TSG101 and FHIT genes occurs frequently in multiple malignancies and in normal tissues and mimics alterations previously described in tumours
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DOI：
10.1038/sj.onc.1201591
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发表时间：
1997-10-23
期刊：
影响因子：
8
通讯作者：
Caldas, C
中科院分区：
文献类型：
--
作者：
Gayther, SA;Barski, P;Caldas, C
在人类乳腺肿瘤中报道了 TSG101 的基因内缺失，TSG101 是小鼠基因 (tsg101) 的人类同源物，具有抑制恶性细胞生长的作用。我们在从多种常见人类恶性肿瘤、EBV 永生化 B 细胞和正常肺实质中分离的 DNA 和 RNA 样本中筛选了 TSG101 的体细胞突变，基因内 TSG101 缺失 RNA 转录本中的 RNA 转录本经常出现在所有类型的样品中，DNA 分析未能显示与同一样品中含有缺失的转录本相对应的基因组重排，大多数转录本缺失的断点与真实或隐藏的剪接位点序列一致，表明它们是由选择性或异常剪接引起的，以前在推定的肿瘤抑制基因中描述了类似的转录本缺失谱 FHIT。我们分析了同一系列RNA样本中的FHIT，并在肿瘤和正常组织中频繁检测到截短的FHIT转录本，此外，在从正常外周血淋巴细胞分离的RNA中分析了来自TSG101、FHIT和其他七个基因的转录本，检测到大的TSC101和FHIT基因内转录本缺失，这些似乎是肿瘤组织中的主要转录本。 “老化”的淋巴细胞。在所分析的其他基因的转录本中未检测到类似的改变。我们的研究结果表明，截短的 TSG101 和 FHIT 转录本在正常和恶性组织中均常见，其中很大一部分可能是异常剪接的结果。虽然我们不能排除 TSG101 和 FHIT 的改变发生在癌症发展过程中，但我们的数据表明，在这种情况下，常见观察到的转录本 异常现象具有误导性。
Intragenic deletions of TSG101, the human homolog of a mouse gene (tsg101) that acts to suppress malignant cell growth, were reported in human breast tumours, We screened TSG101 for somatic mutations in DNA and RNA samples isolated from a variety of common human malignancies, EBV-immortalised B-cells, and normal lung parenchyma, Intragenic TSG101 deletions in RNA transcripts were frequently found in all types of samples, Analysis of DNA failed to show genomic rearrangements corresponding to transcripts containing deletions in the same samples, The breakpoints of most transcript deletions coincide with genuine or cryptic splice site sequences, suggesting that they result from alternative or aberrant splicing, A similar spectrum of transcript deletions has previously been described in the putative tumour suppressor gene FHIT. We analysed FHIT in the same series of RNA samples and detected truncated FHIT transcripts frequently in both tumour and normal tissues, In addition, transcripts from TSG101, FHIT and seven other genes were analysed in RNA isolated from normal peripheral blood lymphocytes, Large TSC101 and FHIT intragenic transcript deletions were detected and these appeared to be the predominant transcript in 'aged' lymphocytes. Similar alterations were not detected in transcripts of the other genes which were analysed, Our findings demonstrate that truncated TSG101 and FHIT transcripts are commonly detected in both normal and malignant tissues and that a significant fraction of these are likely to be the result of aberrant splicing, While we cannot exclude that alterations in TSG101 and FHIT occur during cancer development, our data indicate that in this context the commonly observed transcript abnormalities are misleading.