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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Microsatellite instability in tumor and nonneoplastic colorectal cells from hereditary non-polyposis colorectal cancer and sporadic high microsatellite-instable tumor patients.
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Microsatellite instability in tumor and nonneoplastic colorectal cells from hereditary non-polyposis colorectal cancer and sporadic high microsatellite-instable tumor patients.

机译：遗传性非息肉性结直肠癌和偶发性高微卫星不稳定肿瘤患者的肿瘤和非肿瘤性结直肠细胞中的微卫星不稳定性。

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摘要

Genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) have been frequently studied in various tumor types. Genetic heterogeneity of nonneoplastic cells has not yet been sufficiently investigated. However, genomic instability in normal cells could be a potentially important issue, in particular when these cells are used as reference in LOH and MSI analyses of tumor samples. In order to investigate possible genetic abnormalities in normal colorectal cells of tumor patients, MSI analyses of normal colonic mucosa were performed. Up to 15 different laser-microdissected normal regions containing 50-150 cells were investigated in each of 15 individual microsatellite-stable, sporadic high microsatellite-instable (MSI-H) and hereditary non-polyposis coli cancer (HNPCC) colorectal cancer patients. Frequent MSI and heterogeneity in the MSI pattern were found both in normal and tumor cells from 10 HNPCC and sporadic MSI-H tumor patients whose tumors had defect mismatch repair protein expressions. This observation shows that MSI can also occur in nonneoplastic cells which has to be considered in MSI analyses for molecular HNPCC screening. In addition, considerable genetic heterogeneity was detected in all MSI-H (sporadic and HNPCC) tumors when analyzing five different regions with less than 150 cells, respectively. These differences were not detectable in larger tumor regions containing about 10,000 cells. Thus, heterogeneity of the MSI pattern (e.g. intratumoral MSI) is an important feature of tumors with the MSI-H phenotype. Copyright 2001 S. Karger AG, Basel
机译：遗传变异，如杂合性丧失（LOH）和微卫星不稳定性（MSI）丢失，已在各种肿瘤类型中得到了频繁研究。非肿瘤细胞的遗传异质性尚未得到充分研究。但是，正常细胞的基因组不稳定可能是一个潜在的重要问题，特别是当这些细胞在肿瘤样本的LOH和MSI分析中用作参考时。为了研究肿瘤患者正常结直肠细胞中可能的遗传异常，对正常结肠粘膜进行了MSI分析。在15位个体微卫星稳定，偶发性高位微卫星不稳定（MSI-H）和遗传性非息肉性大肠结肠癌（HNPCC）大肠癌患者中，分别对多达15个包含50-150个细胞的激光显微解剖正常区域进行了研究。在10例HNPCC正常和肿瘤细胞中发现了频繁的MSI和MSI模式的异质性，这些患者的肿瘤具有缺陷错配修复蛋白的表达。该观察结果表明，MSI也可以在非肿瘤细胞中发生，在分子HNPCC筛查的MSI分析中必须考虑到这一点。此外，当分别分析少于150个细胞的五个不同区域时，在所有MSI-H（散发性和HNPCC）肿瘤中检测到相当大的遗传异质性。在包含约10,000个细胞的较大肿瘤区域中无法检测到这些差异。因此，MSI模式（例如肿瘤内MSI）的异质性是具有MSI-H表型的肿瘤的重要特征。版权所有2001 S. Karger AG，巴塞尔

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