Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas.
Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas.
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DOI：
10.5402/2012/576578
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Castresana, Javier S
中科院分区：
文献类型：
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作者：
Munoz, Jorge;Inda, Maria Del Mar;Castresana, Javier S
虽然星形细胞瘤病因中涉及的肿瘤抑制基因的等位基因丢失和突变已被广泛评估，但表观遗传学的作用仍然是一个研究问题。我们通过甲基化特异性 PCR (MSP) 分析了星形细胞瘤样本和细胞系中 5 个肿瘤抑制基因（PTEN、MGMT、RASSF1A、p14(ARF) 和 p16(INK4A)）启动子高甲基化的频率。 RASSF1A 是所有级别的星形细胞瘤样本、细胞系和成人继发性 GBM 中最常见的高甲基化基因。随后是 MGMT。 PTEN 仅在一种 GBM 和一种毛细胞星形细胞瘤以及两种细胞系中显示出轻微的甲基化信号；而p14(ARF)和p16(INK4A)在原发性肿瘤或细胞系中没有显示出任何甲基化的证据。在儿童 GBM 中，RASSF1A 再次成为最常改变的基因，其次是 MGMT； PTEN、p14 和 p16 未显示任何改变。细胞系中 RASSF1A 表达的缺乏或减少与甲基化的存在相关。 RASSF1A 启动子高甲基化可用作继发性 GBM 和儿童 GBM 的诊断标志物。在 PTEN、p14(ARF) 和 p16(INK4A) 等其他基因中，启动子高甲基化可能不是重要的失活机制，这些基因中其他改变（突变、纯合缺失）很普遍。
While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14(ARF), and p16(INK4A)), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14(ARF) and p16(INK4A) did not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14(ARF) and p16(INK4A), in which other alterations (mutations, homozygous deletions) are prevalent.