血管瘤血管内皮生长因子受体KDR基因异常甲基化的研究  

The Abnormal Methylation of Vascular Endothelial Cell Growth Factor Receptor-2（KDR） Gene in In-fancy Hemangioma.

作　　者：杨恩[1] 刘铭[1] 彭强[1] 

机构地区：[1]四川省泸州医学院附属医院小儿外科,四川省泸州市445000

出　　处：《临床小儿外科杂志》2012年第4期268-271,共4页Journal of Clinical Pediatric Surgery

摘　　要：目的通过建立甲基化敏感性高分辨率溶解曲线法（MS-HRM），检测血管内皮生长因子VEGF受体KDR基因启动子区域在不同时期血管瘤、血管畸形及正常皮肤组织中的甲基化状态，初步探讨基因甲基化在血管瘤形成、增生、退化过程中的作用。方法选取不同时期血管瘤石蜡标本48例、血管畸形石蜡标本15例、正常包皮皮肤组织标本8例，分别提取DNA，经亚硫酸氢盐甲基化修饰、纯化、回收DNA，然后用甲基化敏感性高分辨率溶解曲线法（MS-HRM），定量检测不同标本中血管内皮生长因子受体KDR甲基化水平。结果48例血管瘤标本共检出32例不同程度KDR基因启动子区域甲基化（66．67％），其中24例增殖期血管瘤标本中检出21例（87．50％）不同程度甲基化，24例消退期血管瘤标本中检出11例（45．83％）不同程度甲基化，增殖期血管瘤与消退期血管瘤标本中KDR的甲基化程度比较，差异有统计学意义（X^2=9．375，P〈0．05）；15例血管畸形标本中仅检出甲基化程度为0-25％者2例（13．33％），8例正常包皮皮肤组织中检测到1例甲基化0-5％（12．50％）。与血管瘤相比，差异均有统计学意义（P〈0．05，Fisher’确切概率法）。结论血管瘤中血管内皮生长因子受体KDR基因启动子序列CpG岛存在异常甲基化，血管内皮生长因子受体KDR基因异常甲基化可能与血管瘤增生、退化等有关。Objective To investigate the methylation status of vascular endothelial growth factor receptor （VEGFR, KDR） gene in hemangioma, vascular malformation and normal skin tissues by establishing methyla- tion sensitivity high resolution dissolve curve method （MS-HRM）. The role of genetic methylation in prolifera- ting and regressing hemangiomas also will be discussed. Methods 48 different period hemangioma samples, 15 vascular abnormality samples, and 8 normal skin tissue samples were tested respectively. The DNA of sam- ples were extracted, modificated with sulphite methylation. Then, the DNA of samples was purificated and re- cycled and prepared for test. The methylation levels of KDR in all samples were tested by the methylation sensi- tivity high resolution dissolve curve method （MS-HRM）. Results KDR gene methylation were detected posi- tively in 32 hemangioma specimens （66.67%）, including 21 proliferate hemangiomas samples （87.50%） and 11 involuting hemangiomas （45.83%）. There was significant difference between proliferate hemangiomas and involuting hemangiomas in KDR methylation（X^2 = 9. 375, P 〈 0.05 ）. The methylation positive rate of vascular malformation samples was t3.33% （ranged from 0% to 25% ）. The methylation positive rate of normal wrap- ping skin tissues was 12.50 % （ ranged from 0% to 5% ）. The methylation positive rate in hemangioma was significant higher than that in vascular malformation or normal wrapping Skin tissue （P 〈 0.05）. Conclutions Abnormal methylation of KDR expressed in hemangioma which may be associated with hemangioma formation, hyperplasia and degradation.

关 键 词：血管瘤 受体 血管内皮生长因子 基因 

分 类 号：R737.33[医药卫生—肿瘤]