神经纤维瘤病2型患者皮肤神经鞘瘤中的基因丢失  

Loss of NF2 Gene in Neurofibromatosis Type 2－ Associated Cutaneous Schwannomas

作　　者：张军[1] 何筱仙[1] 贾建平[1] 

机构地区：[1]首都医科大学宣武医院神经内科,北京100053

出　　处：《中华皮肤科杂志》2001年第4期257-259,共3页Chinese Journal of Dermatology

摘　　要：目的应用微卫星多态标志研究神经纤维瘤病 2型 (NF2)患者的皮肤神经鞘瘤中 NF2基因丢失情况，以明确其肿瘤的发生机制及 NF2肿瘤抑制基因的特点，为 NF2患者的症状前基因诊断提供依据。方法收集 NF2患者的皮肤肿瘤组织及外周血，提取 DNA，应用微卫星多态标志进行基因型分析。结果 43例皮肤神经鞘瘤在微卫星多态标志 CRYB2， D22S193， NF2CA1， NF2CA3， D22S268， D22S430上显示杂合性丢失的例数分别为 18， 14， 0， 13， 16， 12例。结论建立了在 NF2基因内部及两翼的与 NF2基因紧密连锁的多个微卫星多态标志的杂合性丢失探知 NF2等位基因丢失的方法，再次证实了 NF2基因是一个肿瘤抑制基因。通过对同一患者的多个皮肤神经鞘瘤的研究，发现同一患者的不同肿瘤标本中既有肿瘤存在 NF2基因的丢失，又有肿瘤没有 NF2基因的丢失，说明了这些患者中肿瘤的发展起源于不同的细胞克隆，各肿瘤的基因变异是独立发生的。Objective The loss of NF2 gene in cutaneous schwannomas of neurofibromatosis type 2 patients was investigated in order to explore the tumorigenesis and characteristics of NF2 tumor suppressor gene, and to provide evidence for presymptomatic gene diagnosis for NF2 patients. Methods DNA was extracted from whole blood and frozen tumor tissue, respectively. Genotyping was performed using 6 microsatellite markers flanking or within the NF2 gene: CRYB2－ D22S193－ NF2CA1－ NF2CA3－ D22S268－ D22S430, which is tightly linked to the NF2 gene and analyzed on an ABI Genetic Analyzer 310 after PCR amplification. Results A total of 18,14,0,13,16,12 samples showed loss of heterozygosity at microsatellite markers CRYB2， D22S193， NF2CA1， NF2CA3， D22S268， D22S430 in 43 samples of cutaneous schwannomas, respectively. Conclusions The method for detection of NF2 allelic loss was established. Frequent allelic loss reconfirms that NF2 gene is a tumor suppressor gene. The observation that tumors with or without allelic loss of the NF2 gene exist in the same patient indicates that these tumors are originated from different clones in which genetic alterations occurred independently.

关 键 词：神经纤维瘤 2型 神经鞘瘤 皮肤肿瘤 微随体重复 杂合子丢失 

分 类 号：R730.264[医药卫生—肿瘤]