Mendes-da-Silva P, Moreira A, Duro-da-Costa J, Matias D, Monteiro C
Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal.
Mol Pathol. 2000 Aug;53(4):184-7. doi: 10.1136/mp.53.4.184.
Loss of heterozygosity (LOH) at specific chromosomal regions strongly suggests the existence of tumour suppressor genes at the relevant segment. Frequent LOH on chromosome 5q has been reported in a wide variety of human tumours, including those of the lung. The aim of this study was to screen for LOH and to clarify the location of putative tumour suppressor genes on chromosome 5 implicated in the genesis and/or development of non-small cell lung carcinoma.
Thirty three patients with advanced non-small cell lung carcinoma were screened for LOH with a panel of 21 microsatellite DNA markers spanning the entire chromosome 5, using semi-automated fluorochrome based methodology.
Twenty of the non-small cell lung carcinoma samples displayed LOH for one or more informative locus. LOH involving only 5q was found in 10 of 14 of the informative samples. Deletions involving 5p only were not present in the samples under study. There was no evidence of microsatellite instability in any of the analysed loci. These results indicate the presence of five distinct segments displaying high frequencies of deletion on chromosome 5, namely: 5q11.2-q12.2, 5q15 (D5S644 locus), 5q22.3-q23.1, 5q31.1, and 5q35.3. Eight of 14 samples had simultaneous interstitial deletions in at least two different regions. Moreover, concomitant deletion of three and four distinct regions was displayed in three of 14 and two of 14, respectively, of the informative samples.
Allelic deletion on chromosome 5 is a frequent event in patients with non-small cell lung carcinoma. These results suggest the involvement of these five regions, either independently or simultaneously, in both lung squamous cell carcinoma and lung adenocarcinoma.
特定染色体区域杂合性缺失(LOH)强烈提示相关区段存在肿瘤抑制基因。在包括肺癌在内的多种人类肿瘤中,均报道过5号染色体长臂(5q)频繁发生LOH。本研究旨在筛查LOH,并明确5号染色体上与非小细胞肺癌发生和/或发展相关的假定肿瘤抑制基因的位置。
采用基于荧光染料的半自动方法,用一组覆盖整个5号染色体的21个微卫星DNA标记,对33例晚期非小细胞肺癌患者进行LOH筛查。
20例非小细胞肺癌样本在一个或多个信息位点显示LOH。在14例信息样本中,有10例仅发现5q存在LOH。所研究样本中未出现仅涉及5号染色体短臂(5p)的缺失。在任何分析位点均未发现微卫星不稳定的证据。这些结果表明,5号染色体上存在5个不同区段显示出高频率缺失,即:5q11.2 - q12.2、5q15(D5S644位点)、5q22.3 - q23.1,、5q31.1和5q35.3。14例样本中有8例在至少两个不同区域同时存在间质性缺失。此外,分别有3例(14例中的)和2例(14例中的)信息样本显示同时缺失3个和4个不同区域。
5号染色体上等位基因缺失在非小细胞肺癌患者中是常见事件。这些结果提示这5个区域独立或同时参与肺鳞状细胞癌和肺腺癌的发生。