Combined copy status of 18q21 genes in colorectal cancer shows frequent retention of SMAD7
Combined copy status of 18q21 genes in colorectal cancer shows frequent retention of SMAD7
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DOI：
10.1002/gcc.1140
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发表时间：
2001-07-01
影响因子：
3.7
通讯作者：
Rochlitz, C
中科院分区：
文献类型：
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作者：
Boulay, JL;Mild, G;Rochlitz, C
染色体18 q21带缺失在多种肿瘤中出现的频率很高，尤其是在结直肠癌中。位于该区域的有效肿瘤抑制基因编码转化生长因子β（TGF-β）信号转导物SMAD 2和SMAD 4，并且任一个的失活导致TGF-β介导的细胞生长/凋亡受损。在将SMAD 7分配到18 q21之后，我们首先通过在SMAD 2和SMAD 4之间对SMAD 7进行遗传定位来细化SMAD 7基因在该区域内的位置。此外，为了比较这三个SMAD基因在结直肠癌中的遗传改变的各自频率，我们对来自结直肠肿瘤活检材料的DNA样品上的这些基因中的每一个的拷贝状态进行了大规模的评估。在233个DNA样本的子集中，SMAD 4、SMAD 2和附近的基因DCC显示出高缺失率（分别为66%、64%和59%），而SMAD 7仅在48%的肿瘤中缺失。出乎意料的是，我们发现了一些基因重复; SMAD 7似乎比其他三个基因（4-7%）更频繁地扩增（10%）。每个肿瘤中SMAD基因的汇编数据显示，最常见的组合（占所有肿瘤的26%）包括与正常二倍体甚至SMAD 7重复相关的SMAD 2和SMAD 4同时缺失。由于SMAD 7通常会抵消TGF-β信号传导中的SMAD 2和SMAD 4，我们假设肿瘤可能不会从同时的SMAD 7失活中受益，从而施加选择性压力来保留甚至复制SMAD 7基因。(C)2001年威利-利斯。Inc.
Deletions of chromosome band 18q21 appear with very high frequency in a variety of carcinomas, especially in colorectal cancer, Potent tumor suppressor genes located in this region encode transforming growth factor beta (TGF-beta) signal transducers SMAD2 and SMAD4, and inactivation of either one leads to impaired TGF-beta -mediated cell growth/apoptosis. Following the assignment of SMAD7 to 18q21, we first refined the SMAD7 gene position within this region by genetically mapping SMAD7 between SMAD2 and SMAD4. Further, to compare the respective frequencies of genetic alterations of these three SMAD genes in colorectal cancer, we undertook a large-scale evaluation of the copy status of each of these genes on DNA samples from colorectal tumor biopsy material. Among a subset of 233 DNA samples for which data were available for all four genes, SMAD4, SMAD2, and the nearby gene DCC showed high deletion rates (66%, 64%, and 59%, respectively), whereas SMAD7 was deleted in only 48% of the tumors. Unexpectedly, we found some gene duplications; SMAD 7 appears to be more frequently amplified (10%) than the three other genes (4-7%). Compiled data for SMAD genes in each tumor show that the most common combination (26% of all the tumors) consists of the simultaneous deletions of SMAD2 and SMAD4 associated with normal diploidy or even duplication of SMAD7. Since SMAD7 normally counteracts SMAD2 and SMAD4 in TGF-beta signaling, we hypothesize that the tumor might not benefit from simultaneous SMAD7 inactivation, thereby exerting selective pressure to retain or even to duplicate the SMAD7 gene. (C) 2001 Wiley-Liss. Inc.