Arslan Sulhattin, Dogan Tamer, Koksal Binnur, Yildirim Malik Ejder, Gumus Cesur, Elagoz Sahenda, Akkurt Ibrahim, Ozdemir Oztürk
Department of Thorax Diseases, Faculty of Medicine, Cumhuriyet University 58140 Sivas/Turkey.
Lung India. 2008 Oct;25(4):148-51. doi: 10.4103/0970-2113.45279.
Non-small cell lung carcinoma is an aggressive phenomenon and the epigenetical alterations of some tumor supressor genes have been reported for the different tumor types.
It is presented a case report concerning a 43 years old male with NSCLC on the lower segment of the right lung. The patient underwent a diag-nostic excisional thin-needle biopsy and after the histological confirmation. We examined the promoter methylation status of some distinct tumor supressor genes in tumoral and blood tissues of the case after sodium bisulfite conversion and DNA amplification with methylation specific multiplex PCR technique. Both tissues were also searched for G to A transitions in codons 12 and 13 of the K-ras proto-oncogene.
Tumor specimen showed fully methyl pattern profiles for the SFRP2, p16, DAPK1 and partially hyper-methylated profile for the p53 and MGMT genes in this case with non-small lung carci-noma. Blood speicemen showed normal hypomethylated profiles for all studied TS genes. The K-ras proto-oncogene was in normal structure both in blood and tumoral spiecemens that examined.
Results indicate that genes exhibit tumor suppressor activi-ties in blood, but exhibit epigenetic inactivation in carcinoma cell. These findings strongly support the hypothesis that epigenetic mechanisms may play an important role in the non-small cell lung carcinogenesis in human.
非小细胞肺癌是一种侵袭性疾病,已有报道不同肿瘤类型中一些肿瘤抑制基因发生表观遗传学改变。
本文报告一例43岁男性右下肺非小细胞肺癌患者。患者接受了诊断性细针切除活检,经组织学确诊后,我们采用甲基化特异性多重PCR技术,在亚硫酸氢钠转化和DNA扩增后,检测了该病例肿瘤组织和血液组织中一些不同肿瘤抑制基因的启动子甲基化状态。同时还在K-ras原癌基因的第12和13密码子中寻找G到A的转换。
在该非小细胞肺癌病例中,肿瘤标本显示SFRP2、p16、DAPK1基因呈现完全甲基化模式,p53和MGMT基因呈现部分高甲基化模式。血液标本中所有研究的肿瘤抑制基因均显示正常的低甲基化模式。所检测的血液和肿瘤标本中K-ras原癌基因结构均正常。
结果表明,这些基因在血液中具有肿瘤抑制活性,但在癌细胞中表现为表观遗传失活。这些发现有力地支持了表观遗传机制可能在人类非小细胞肺癌发生中起重要作用这一假说。