Ishwad C S, Ferrell R E, Rossie K M, Appel B N, Johnson J T, Myers E N, Law J C, Srivastava S, Gollin S M
Department of Human Genetics, University of Pittsburgh, PA 15261, USA.
Int J Cancer. 1995 Oct 20;64(5):332-5. doi: 10.1002/ijc.2910640509.
Generalized genomic instability, detected as somatic changes in allele sizes at microsatellite loci in tumors compared to peripheral lymphocyte DNA, is a recently recognized mechanism of mutation in cancer. Such instability results from the somatic loss of DNA mismatch repair capability. Germ-line mutations at DNA mismatch repair loci confer susceptibility to colon cancer in hereditary non-polyposis colorectal cancer. Somatic loss of DNA mismatch repair has been reported in a large variety of other tumor types. Our goal was to determine the frequency of microsatellite instability in a large series of oral tumors. Out of 91 tumors analyzed for microsatellite instability, 6 (7%) showed microsatellite instability. Instability was observed at multiple loci with a range of 50-74% of loci affected. Alterations include both increase (74%) and decrease (26%) in allele sizes. The proportion of alleles affected ranged from 30-58% of all alleles. Our data suggest that somatic genomic instability plays a role in the pathogenesis of a small subset of oral tumors.
与外周血淋巴细胞DNA相比，肿瘤微卫星位点等位基因大小的体细胞变化所检测到的广义基因组不稳定性，是一种最近才被认识到的癌症突变机制。这种不稳定性是由于DNA错配修复能力的体细胞丧失所致。DNA错配修复位点的种系突变使遗传性非息肉病性结直肠癌患者易患结肠癌。在许多其他肿瘤类型中也有DNA错配修复体细胞丧失的报道。我们的目标是确定一大系列口腔肿瘤中微卫星不稳定性的频率。在分析微卫星不稳定性的91个肿瘤中，有6个（7%）显示出微卫星不稳定性。在多个位点观察到不稳定性，受影响的位点范围为50-74%。改变包括等位基因大小的增加（74%）和减少（26%）。受影响的等位基因比例占所有等位基因的30-58%。我们的数据表明，体细胞基因组不稳定性在一小部分口腔肿瘤的发病机制中起作用。
