Distinct patterns of microsatellite instability are seen in tumours of the urinary tract
Distinct patterns of microsatellite instability are seen in tumours of the urinary tract
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DOI：
10.1038/sj.onc.1206964
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发表时间：
2003-11-27
期刊：
影响因子：
8
通讯作者：
Meuth, M
中科院分区：
文献类型：
--
作者：
Catto, JWF;Azzouzi, AR;Meuth, M
迄今为止，在人类癌症中已经描述了两种形式的微卫星不稳定性（MSI）。遗传性非息肉病性结肠癌（HNPCC）的MSI是由DNA错配修复缺陷（MMR）引起的，并由单核苷酸和二核苷酸重复微卫星定义。第二种不稳定性在选择性四核苷酸重复序列（EMAST;选择性四核苷酸的微卫星改变）中最明显。虽然MSI在膀胱癌中很少发生，但EMAST很常见。显示MSI比例最大的散发性肿瘤是HNPCC中最常见的肿瘤。虽然膀胱癌在HNPCC中不常见，但上尿路肿瘤（UTT）是常见的。先前发现膀胱癌中MSI的发生率较低，我们试图确定上下尿路移行细胞癌（TCC）中MSI和EMAST的相对水平。微卫星分析进行了10个单，二核苷酸和八个四核苷酸位点，在89膀胱和71 UTT TCC。对比模式的不稳定性被视为泌尿系肿瘤。在膀胱癌中，MSI罕见，EMAST常见。EMAST的存在与肿瘤分级、分期、后续结果或MMR蛋白的免疫组化表达无关。在UTT中，虽然MSI经常发生，但EMAST的发生率低于膀胱癌。当比较上尿路和下尿路的TCC时，MSI-H在UTT中更常见，EMAST在膀胱癌中更常见。我们的研究结果表明，对于结直肠癌，MSI的模式随泌尿道的位置而变化。此外，我们已经证实MSI和EMAST是MSI的离散形式，并且EMAST的存在不影响肿瘤表型。
To date, two forms of microsatellite instability (MSI) have been described in human cancer. MSI typical of hereditary nonpolyposis colon cancer (HNPCC), is due to deficient DNA mismatch repair (MMR) and is defined with mono- and dinucleotide repeat microsatellites. A second variety of instability is best seen at selective tetranucleotide repeats (EMAST; elevated microsatellite alterations at select tetranucleotides). While MSI occurs infrequently in bladder cancers, EMAST is common. Sporadic tumours with the largest proportion showing MSI are those found most frequently in HNPCC kindreds. While bladder cancer is not frequently seen in HNPCC, upper urinary tract tumours (UTTs) are. Having previously found a low frequency of MSI in bladder cancer, we sought to determine the relative levels of MSI and EMAST in transitional cell carcinoma (TCC) of the upper and lower urinary tracts. Microsatellite analysis was performed at 10 mono- and dinucleotide and eight tetranucleotide loci, in 89 bladder and 71 UTT TCC. Contrasting patterns of instability were seen in urinary tumours. In bladder cancer, MSI was rare and EMAST was common. The presence of EMAST was not related to tumour grade, stage, subsequent outcome or immunohistochemical expression of the MMR proteins. In UTT, while MSI occurred frequently, EMAST was seen less frequently than in bladder cancer. When TCC of the upper and lower urinary tracts are compared, MSI-H is more frequent in UTT and EMAST more frequent in bladder cancer. Our findings show that, as for colorectal cancer, the pattern of MSI varies with location in the urinary tract. In addition, we have confirmed that MSI and EMAST are discrete forms of MSI, and that the presence of EMAST does not affect tumour phenotype.