Structure and expression of the human FHIT gene in normal and tumor cells.
Structure and expression of the human FHIT gene in normal and tumor cells.
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发表时间：
1997-02
期刊：
影响因子：
11.2
通讯作者：
T. Druck;P. Hadaczek;Tie-bo Fu;M. Ohta;Z. Siprashvili;R. Baffa;M. Negrini;K. Kastury;M. L. Veronese;D. Rosen;J. Rothstein;P. Mccue;M. Cotticelli;H. Inoue;C. Croce;K. Huebner
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文献类型：
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作者：
T. Druck;P. Hadaczek;Tie-bo Fu;M. Ohta;Z. Siprashvili;R. Baffa;M. Negrini;K. Kastury;M. L. Veronese;D. Rosen;J. Rothstein;P. Mccue;M. Cotticelli;H. Inoue;C. Croce;K. Huebner
FHIT基因由10个外显子在1.1-kb转录本中编码，包含约1 Mb的基因组DNA，其包括遗传性RCC t（3;8）易位在3p14.2处的断裂、FRA 3B常见脆性区和各种癌症衍生细胞系中的纯合缺失。因为其中一些遗传标志（例如，t（3; 8）未翻译的FHIT外显子3和4之间的断裂，包括外显子4和5之间的病毒整合位点的主要脆性区，以及内含子5中的癌细胞纯合缺失）不一定影响编码外显子，但明显影响基因产物的表达，我们在超过10种肿瘤衍生细胞系中详细检测了FHIT基因座及其表达，以阐明异常表达的潜在机制。我们观察到一些细胞系明显连续的大纯合缺失，其中包括一个或多个编码外显子;细胞系不连续缺失，其中一些包括或排除编码外显子;和细胞系表现出杂合和/或纯合缺失，通过Southern印迹分析特定外显子的存在。大多数表现出基因组改变的细胞系显示FHIT转录物的改变和Fhit蛋白的缺失或减少。
The FHIT gene, encoded by 10 exons in a 1.1-kb transcript, encompasses approximately 1 Mb of genomic DNA, which includes the hereditary RCC t(3;8) translocation break at 3p14.2, the FRA3B common fragile region, and homozygous deletions in various cancer-derived cell lines. Because some of these genetic landmarks (e.g., the t(3;8) break between untranslated FHIT exons 3 and 4, a major fragile region that includes a viral integration site between exons 4 and 5, and cancer cell homozygous deletions in intron 5) do not necessarily affect coding exons and yet apparently affect expression of the gene product, we examined the FHIT locus and its expression in detail in more than 10 tumor-derived cell lines to clarify mechanisms underlying aberrant expression. We observed some cell lines with apparently continuous large homozygous deletions, which included one or more coding exons; cell lines with discontinuous deletions, some of which included or excluded coding exons; and cell lines that exhibited heterozygous and/or homozygous deletions, by Southern blot analysis for the presence of specific exons. Most of the cell lines that exhibited genomic alterations showed alteration of FHIT transcripts and absence or diminution of Fhit protein.