Krakowczyk Lukasz, Strzelczyk Joanna K, Adamek Brygida, Zalewska-Ziob Marzena, Arendt Jerzy, Półtorak Stanisław, Maciejewski Bogusław, Wiczkowski Andrzej
Department of General Biology, Zabrze, Medical University of Silesia in Katowice, Katowice, Poland.
Med Sci Monit. 2008 Oct;14(10):BR219-25.
Colorectal cancer, one of the most aggressive cancers, occurs with a high incidence in most countries. The usual treatment is surgery and subsequent chemotherapy and radiotherapy. Cancer development and progression is dictated by series of alterations in genes such as tumor suppressor genes, DNA repair genes, oncogenes and others. In colorectal carcinogenesis disturbances different from mutations called an epigenetic regulation are also taken into consideration. Epigenetics is defined as a modifications of the genome, heritable during cell division, which do not involve a change in the DNA sequence. In our study we analyzed methylation of CpG islands in the MGMT and p16 genes in sporadic colorectal cancers and normal corresponding colonic mucosa.
MATERIAL/METHODS: Fresh tissue samples were obtained from 68 patients (age of 23 to 81 years) with primary colorectal adenocarcinoma and corresponding normal tissues. We used methylation-specific polymerase chain reaction (MSP) for analysis of the methylation status of MGMT and p16.
Methylation of MGMT and p16 was detected in 59% and 53% of tumors, respectively. In corresponding normal colonic mucosa methylation of MGMT was detected in 20% and p16 in 18%. The normal colon mucosa obtained from younger patients (age of <65 years) showed less methylation frequency as compared with the normal mucosa from the older ones (age of >65 years).
The older age and female gender are generally associated with higher methylation levels for most CpG islands in normal colonic mucosa. These results indicate that MGMT and/or p16 aberrant methylation may play an important role in colorectal cancer.
结直肠癌是侵袭性最强的癌症之一，在大多数国家发病率都很高。常规治疗方法是手术以及后续的化疗和放疗。癌症的发生和发展是由一系列基因改变所决定的，如肿瘤抑制基因、DNA修复基因、癌基因等。在结直肠癌发生过程中，除了称为表观遗传调控的与突变不同的干扰因素也被考虑在内。表观遗传学被定义为基因组的修饰，在细胞分裂过程中可遗传，且不涉及DNA序列的改变。在我们的研究中，我们分析了散发性结直肠癌及相应正常结肠黏膜中MGMT和p16基因的CpG岛甲基化情况。
材料/方法：从68例（年龄23至81岁）原发性结肠腺癌患者及相应正常组织中获取新鲜组织样本。我们使用甲基化特异性聚合酶链反应（MSP）分析MGMT和p16的甲基化状态。
MGMT和p16甲基化分别在59%和53%的肿瘤中被检测到。在相应的正常结肠黏膜中，MGMT甲基化在20%中被检测到，p16甲基化在18%中被检测到。与老年患者（年龄>65岁）的正常黏膜相比，年轻患者（年龄<65岁）的正常结肠黏膜甲基化频率较低。
在正常结肠黏膜中，老年和女性性别通常与大多数CpG岛的较高甲基化水平相关。这些结果表明，MGMT和/或p16异常甲基化可能在结直肠癌中起重要作用。
