The ACIN1 gene is hypermethylated in early stage lung adenocarcinoma
The ACIN1 gene is hypermethylated in early stage lung adenocarcinoma
复制标题
DOI：
10.1097/01243894-200602000-00010
复制
发表时间：
2006-02-01
影响因子：
20.4
通讯作者：
Noguchi, Masayuki
中科院分区：
文献类型：
--
作者：
Shu, Yujian;Iijima, Tatsuo;Noguchi, Masayuki
引言和假设：近年来，许多研究在全基因组范围内寻找癌症中差异甲基化的基因。我们假设某些基因的CpG岛特征性异常高甲基化可能存在于肺腺癌的早期阶段，并且这种改变可能有助于早期肺腺癌的检测和治疗。 方法：对源自非典型腺瘤性增生（PL16T）和同一患者支气管切除端（PL16B）的一对永生化细胞系进行异常和异常检测。通过甲基化 CpG 岛扩增和抑制消减杂交方法的组合，差异性高甲基化 DNA 片段。结果：从 229 个克隆中，我们选择了 15 个基因组区域符合 CpG 岛标准的片段。我们鉴定了一个基因，即凋亡染色质浓缩诱导物 1 (ACIN1)，该基因在 PL16T 中高度甲基化。与正常肺组织 (9/37, 24%, p < 0.05) 相比，在小型腺癌（2 cm 或更小）中发现从 ACIN1 基因分离的 DNA 片段 5' 端位点的高甲基化频率较高（30/37, 81%）。有趣的是，ACIN1 的高甲基化在不具有细支气管肺泡癌 (BAC) 成分的正常腺癌中相对频繁地检测到 (7/16, 44%)，但在具有 BAC 成分的正常腺癌中很少见 (2/21, 10%, P < 0.05)。 结论：我们在早期肺腺癌中发现了 ACIN1 基因的高甲基化。甲基化状态在肺腺癌的发生和恶性转化中的作用需要澄清。
Introduction and Hypothesis: In recent years, many studies have performed genome-wide searching for differentially methylated genes in cancer. We hypothesized that characteristic aberrant hypermethylation of CpG islands of certain genes may exist in the early stages of lung adenocarcinoma and that such alterations may be useful in the detection and treatment of early lung adenocarcinoma.Methods: A pair of immortalized cell lines originating from atypical adenomatous hyperplasia (PL16T) and from the resected end of the bronchus of the same patient (PL16B) was searched for aberrantly and differentially hypermethylated DNA fragments by a combination of the methylated CpG island amplification and suppression subtractive hybridization methods.Results: From 229 clones, we selected 15 fragments that had a genomic region meeting the criteria for a CpG island. We identified a gene, apoptotic chromatin condensation inducer 1 (ACIN1), that was hypermethylated in PL16T. A higher frequency of hypermethylation at a locus at the 5' end of the DNA fragment isolated from the ACIN1 gene was found in small-sized adenocarcinoma (2 cm or less) (30/37, 81%) compared with normal lung tissue (9/37, 24%, p < 0.05). Interestingly, hypermethylation of ACIN1 was detected relatively frequently in the normal counterpart of adenocarcinoma without bronchioloalveolar carcinoma (BAC) component (7/16, 44%), but was rare in the normal counterpart of adenocarcinoma with BAC component (2/21, 10%, P < 0.05).Conclusions: We found hypermethylation of the ACIN1 gene in early stage lung adenocarcinoma. The role of methylation status in the development and malignant transformation of lung adenocarcinoma requires clarification.