Roa Juan Carlos, Anabalón Leonardo, Tapia Oscar, Martínez Javier, Araya Juan Carlos, Villaseca Miguel, Guzmán Pablo, Roa Iván
Departamento de Anatomía Patológica, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile.
Rev Med Chil. 2004 Sep;132(9):1069-77.
Genomic DNA methylation, mutations and allelic deletions explain the inactivation of genes involved in cell proliferation and cell cycle control mechanisms.
To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with breast cancer and the relationship with its biological behavior.
Seventy fresh-frozen breast cancer samples were selected. The methylation specific PCR (MSP) test was used to analyze promoter methylation status for genes CDKN2A (p16), hMLH1, APC, CDH1 (Cadherin E) and FHIT.
We found methylation in at least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. The frequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHT were 41.4%, 11.4%, 52.9%, 70% and 42.9%, respectively. We found a relationship between CDKN2A methylatlon and better survival (p=0.002). CDH1 methylation and poor histological differentiation (p=0.007), hMLH1 methylation and non-Mapuche ethnicity (p=-0.03), APC methylation and larger tumor size (p<0.05), FHIT methylatton and lack of estrogen rectptor IHC expression (p<0.05).
The high frequency of promoter methylation in patients with breast cancer confirms its role in breast carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search of new criteria for clinical and therapeutic decision making.
基因组DNA甲基化、突变和等位基因缺失可解释参与细胞增殖和细胞周期调控机制的基因失活。
分析乳腺癌患者中与不同致癌机制相关的重要基因的甲基化模式及其与生物学行为的关系。
选取70例新鲜冷冻乳腺癌样本。采用甲基化特异性PCR（MSP）检测分析CDKN2A（p16）、hMLH1、APC、CDH1（钙黏蛋白E）和FHIT基因的启动子甲基化状态。
我们发现88%的病例中至少有一个研究基因发生甲基化，40.5%的病例中有3个或更多基因发生甲基化。CDKN2A、hMLH1、APC、CDH1和FHT启动子高甲基化的频率分别为41.4%、11.4%、52.9%、70%和42.9%。我们发现CDKN2A甲基化与较好的生存率相关（p = 0.002）。CDH1甲基化与组织学分化差相关（p = 0.007），hMLH1甲基化与非马普切族裔相关（p = -0.03），APC甲基化与肿瘤较大相关（p < 0.05），FHIT甲基化与雌激素受体免疫组化表达缺失相关（p < 0.05）。
乳腺癌患者启动子甲基化的高频率证实了其在乳腺癌发生中的作用。所研究基因甲基化模式改变的发现及其与预后因素的关联是寻找临床和治疗决策新标准的有用工具。
