Kettunen E, Aavikko M, Nymark P, Ruosaari S, Wikman H, Vanhala E, Salmenkivi K, Pirinen R, Karjalainen A, Kuosma E, Anttila S
Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland.
Br J Cancer. 2009 Apr 21;100(8):1336-42. doi: 10.1038/sj.bjc.6605012. Epub 2009 Mar 31.
Five to seven percent of lung tumours are estimated to occur because of occupational asbestos exposure. Using cDNA microarrays, we have earlier detected asbestos exposure-related genomic regions in lung cancer. The region at 2p was one of those that differed most between asbestos-exposed and non-exposed patients. Now, we evaluated genomic alterations at 2p22.1-p16.1 as a possible marker for asbestos exposure. Lung tumours from 205 patients with pulmonary asbestos fibre counts from 0 to 570 million fibres per gram of dry lung, were studied by fluorescence in situ hybridisation (FISH) for DNA copy number alterations (CNA). The prevalence of loss at 2p16, shown by three different FISH probes, was significantly increased in lung tumours of asbestos-exposed patients compared with non-exposed (P=0.05). In addition, a low copy number loss at 2p16 associated significantly with high-level asbestos exposure (P=0.02). Furthermore, 27 of the tumours were studied for allelic imbalances (AI) at 2p22.1-p16.1 using 14 microsatellite markers and also AI at 2p16 was related to asbestos exposure (P=0.003). Our results suggest that alterations at 2p16 combined with other markers could be useful in diagnosing asbestos-related lung cancer.
据估计，5%至7%的肺部肿瘤是由于职业性接触石棉所致。我们此前利用cDNA微阵列在肺癌中检测到了与石棉接触相关的基因组区域。2p区域是石棉接触患者和未接触患者之间差异最大的区域之一。现在，我们评估了2p22.1-p16.1处的基因组改变作为石棉接触的一种可能标志物。对205例肺部石棉纤维计数为每克干肺0至5.7亿根纤维的患者的肺部肿瘤进行了荧光原位杂交（FISH）研究，以检测DNA拷贝数改变（CNA）。与未接触石棉的患者相比，三种不同FISH探针显示的2p16缺失在石棉接触患者的肺部肿瘤中显著增加（P=0.05）。此外，2p16处的低拷贝数缺失与高水平石棉接触显著相关（P=0.02）。此外，使用14个微卫星标记研究了27个肿瘤在2p22.1-p16.1处的等位基因失衡（AI），并且2p16处的AI也与石棉接触有关（P=0.003）。我们的结果表明，2p16处的改变与其他标志物相结合可能有助于诊断石棉相关肺癌。
