胃肠道胰腺神经内分泌肿瘤中 LINE1 甲基化模式的位点和分级特异性多样性。

Site- and grade-specific diversity of LINE1 methylation pattern in gastroenteropancreatic neuroendocrine tumours.

机构信息

Institute of Pathology, Ruhr University Bochum, Bochum, Germany.

出版信息

Anticancer Res. 2012 Sep;32(9):3699-706.

Abstract

BACKGROUND

Recent data indicate that gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have a hypomethylated long interspersed element (LINE1) promoter. To answer the question, of whether LINE1 may be of value in assessing the malignant potential of GEP-NETs, we analysed LINE1 methylation in different organs.

MATERIALS AND METHODS

A total of 58 GEP-NETs of gastric (n=14), pancreatic (n=15), small intestine (n=17), appendix (n=8), colorectal (n=4) and non-neoplastic tissues were analysed using DNA isolation, bisulphite-treatment and pyrosequencing.

RESULTS

LINE1 hypomethylation was detected in 50% of gastric, 100% pancreatic, 82% small intestine, 87.5% appendix and 100% colorectal NETs. G1 (p<0.001) and G2 (p<0.05) colorectal, and G1 (p<0.001) and G2 (p<0.001) pancreatic NETs exhibited significant LINE1 hypomethylation compared with non-neoplastic tissues. Higher rates of LINE1 hypomethylation in G2 pancreatic NETs than in G1 NETs (p<0.05) were observed. NETs exhibited a significantly lower frequency of hypomethylation in cases with lymph node metastases (p<0.05).

CONCLUSION

LINE1 hypomethylation may serve as a marker of tumour grade and lymph node metastasis.

摘要

背景

最近的数据表明，胃肠胰神经内分泌肿瘤（GEP-NETs）存在低甲基化的长散布元件（LINE1）启动子。为了回答 LINE1 是否可用于评估 GEP-NETs 的恶性潜能这一问题，我们分析了不同器官中的 LINE1 甲基化情况。

材料与方法

使用 DNA 分离、亚硫酸氢盐处理和焦磷酸测序，对 58 例胃（n=14）、胰腺（n=15）、小肠（n=17）、阑尾（n=8）、结直肠（n=4）和非肿瘤组织的 GEP-NET 进行分析。

结果

在 50%的胃 NET、100%的胰腺 NET、82%的小肠 NET、87.5%的阑尾 NET 和 100%的结直肠 NET 中检测到 LINE1 低甲基化。与非肿瘤组织相比，G1（p<0.001）和 G2（p<0.05）结直肠 NET 以及 G1（p<0.001）和 G2（p<0.001）胰腺 NET 均显示出显著的 LINE1 低甲基化。在 G2 胰腺 NET 中，LINE1 低甲基化的比例高于 G1 NET（p<0.05）。在伴有淋巴结转移的病例中，NETs 的低甲基化频率显著降低（p<0.05）。