Nunn J, Nagini S, Risk J M, Prime W, Maloney P, Liloglou T, Jones A S, Rogers S R, Gosney J R, Woolgar J, Field J K
Molecular Genetics and Oncology Group, Department of Clinical Dental Science, The University of Liverpool, Liverpool L69 3BX, UK.
Oral Oncol. 2003 Feb;39(2):115-29. doi: 10.1016/s1368-8375(02)00028-3.
Squamous cell carcinoma of the head and neck (SCCHN) is one of the 10 most frequently occurring cancers in the world. Defective mismatch repair, as exhibited by the phenomenon of microsatellite instability, has been observed in SCCHN although no reports of mismatch repair gene mutations or altered protein expression have been published. In a variety of microsatellite instability (MSI) positive cancers where mutations in the mismatch repair (MMR) genes were not observed, allelic imbalance at the loci of the MMR genes was prevalent.
To investigate whether allelic imbalance at the MMR genetic loci contributes to the development of SCCHN.
35 matched normal/tumour SCCHN pairs were studied using 29 microsatellite markers located within and adjacent to six known DNA mismatch repair genes. In addition, mutational analysis and protein expression of hMSH2 and hMLH1 were investigated.
We demonstrated that 36 and 17% of the analysed SCCHN specimens exhibited allele imbalance at the hMLH1 and hMSH3 genetic loci, respectively. Allelic instability at these two loci was found to be correlated with the MSI status of the SCCHN tumours. Allelic instability was found to be uncommon at the other MMR gene loci analysed. One mutation was found in hMSH2 and none in hMLH1 in this series of tumours. 23 of 24 (96%) of the examined SCCHN tumours showed reduced expression of either hMSH2 or hMCH1 genes. Allelic instability in the MMR genes, hMLH1 and hMSH3, is proposed to be involved in the aetiology of SCCHN tumours.
头颈部鳞状细胞癌（SCCHN）是全球十大常见癌症之一。尽管尚未发表错配修复基因突变或蛋白表达改变的报告，但在SCCHN中已观察到微卫星不稳定性现象所表现出的错配修复缺陷。在多种未观察到错配修复（MMR）基因突变的微卫星不稳定性（MSI）阳性癌症中，MMR基因位点的等位基因失衡普遍存在。
研究MMR基因位点的等位基因失衡是否有助于SCCHN的发生发展。
使用位于6个已知DNA错配修复基因内部及相邻区域的29个微卫星标记，对35对匹配的正常/肿瘤SCCHN样本进行研究。此外，还研究了hMSH2和hMLH1的突变分析及蛋白表达情况。
我们证明，分别有36%和17%的分析SCCHN标本在hMLH1和hMSH3基因位点表现出等位基因失衡。发现这两个位点的等位基因不稳定性与SCCHN肿瘤的MSI状态相关。在分析的其他MMR基因位点，等位基因不稳定性并不常见。在这一系列肿瘤中，hMSH2发现1个突变，hMLH1未发现突变。24个检测的SCCHN肿瘤中有23个（96%）显示hMSH2或hMCH1基因表达降低。MMR基因hMLH1和hMSH3中的等位基因不稳定性被认为参与了SCCHN肿瘤的病因学。
