Pócza T, Krenács T, Turányi E, Csáthy J, Jakab Z, Hauser P
Peter Hauser, 2nd Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, H-1094 Budapest, Hungary, phone: +36(1)2151380, fax: +36(1)2151381, e-mail:
Folia Neuropathol. 2016;54(2):105-13. doi: 10.5114/fn.2016.60365.
Epigenetic alterations have been implicated in cancer development. DNA methylation modulates gene expression, which is catalyzed by DNA methyltransferases (DNMTs). The objective of our study was to evaluate expression of DNMTs in medulloblastoma and analyze its correlation with clinical features. Nuclear expression of DNMT1, DNMT3A and DNMT3B was analyzed in human primary medulloblastoma of 44 patients using immunohistochemistry. Correlation of expression of DNMT levels with classical histological subtypes, novel molecular subgroups and survival of patients was analyzed. Elevated expression of DNMT1, DNMT3A and DNMT3B was observed in 63.64%, 68.18% and 72.73% of all cases, respectively. None of them showed a correlation with classical histology or survival. Concerning molecular subtypes, significantly higher expression of DNMT1 was observed in the SHH group compared to non-SHH samples (p = 0.02), but without significant difference in DNMT3A or DNMT3B levels between any subtypes. In conclusion, DNMT1, DNMT3A and DNMT3B are highly expressed in human medulloblastoma samples, suggesting that promoter hypermethylation may play a role in medulloblastoma development. Demethylation of tumor suppressor gene promoters may be considered as a possible future target in therapy of medulloblastoma.
表观遗传改变与癌症发展有关。DNA甲基化调节基因表达，这一过程由DNA甲基转移酶（DNMTs）催化。我们研究的目的是评估DNMTs在髓母细胞瘤中的表达，并分析其与临床特征的相关性。使用免疫组织化学方法分析了44例人类原发性髓母细胞瘤中DNMT1、DNMT3A和DNMT3B的核表达情况。分析了DNMT水平表达与经典组织学亚型、新型分子亚组以及患者生存率之间的相关性。在所有病例中，分别有63.64%、68.18%和72.73%的病例观察到DNMT1、DNMT3A和DNMT3B表达升高。它们均与经典组织学或生存率无关。关于分子亚型，与非SHH样本相比，SHH组中DNMT1的表达显著更高（p = 0.02），但各亚型之间DNMT3A或DNMT3B水平无显著差异。总之，DNMT1、DNMT3A和DNMT3B在人类髓母细胞瘤样本中高表达，提示启动子高甲基化可能在髓母细胞瘤发展中起作用。肿瘤抑制基因启动子的去甲基化可能被视为未来髓母细胞瘤治疗的一个潜在靶点。
