Distinct 3p21.3 deletions in lung cancer and identification of a new human semaphorin.

Distinct 3p21.3 deletions in lung cancer and identification of a new human semaphorin.
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DOI:
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发表时间:
1996-03
期刊:
影响因子:
8
通讯作者:
J. Roche;F. Boldog;Misi Robinson;Linda Robinson;Marileila Varella-Garcia;M. Swanton;B. Waggoner;R. Fishel;Wilbur A. Franklin;R. Gemmill;H. Drabkin
J. Roche;F. Boldog;Misi Robinson;Linda Robinson;Marileila Varella-Garcia;M. Swanton;B. Waggoner;R. Fishel;Wilbur A. Franklin;R. Gemmill;H. Drabkin
中科院分区:
医学1区
文献类型:
--
作者:
J. Roche;F. Boldog;Misi Robinson;Linda Robinson;Marileila Varella-Garcia;M. Swanton;B. Waggoner;R. Fishel;Wilbur A. Franklin;R. Gemmill;H. Drabkin

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染色体3p丢失是肺癌发病机制中的关键事件。肺癌细胞系中涉及GNAI2的重叠纯合3p21.3缺失被表征,并发现涉及基因组不稳定区域。从GNAI2缺失区分离到一种新的广泛表达的脑信号蛋白,H.SemaIV。降低的H.SemaIV表达允许鉴定具有以异质方式发生的亚显微镜或更大的基因座缺失的另外的细胞系。我们还证明了一个独特的3p21.3纯合缺失区的存在下,邻近的DNA错配修复基因,hMLH1,并确定直接肿瘤中的缺失。这似乎代表了在直接肺肿瘤中影响3p的纯合缺失的第一个证明。
Loss of chromosome 3p is a critical event in the pathogenesis of lung cancer. Overlapping homozygous 3p21.3 deletions in lung cancer cell lines involving GNAI2 were characterized and found to involve a region of genomic instability. A new widely expressed Semaphorin, H.SemaIV, was isolated from the GNAI2 deletion region. Reduced H.SemaIV expression allowed identification of additional cell lines with submicroscopic or larger deletions of the locus which occurred in a heterogeneous manner. We also demonstrate the presence of a distinct 3p21.3 homozygous deletion region, adjacent to the DNA mismatch repair gene, hMLH1, and identified deletions in direct tumors. This appears to represent one of the first demonstrations of homozygous deletions affecting 3p in direct lung tumors.