听神经瘤中NF2基因突变分析

摘要

目的明确中国人群听神经瘤中NF2基因突变和大片段缺失比例及其意义.方法收集2007年1月至2010年12月期间84例散发型听神经瘤标本组织,采用标准测序检测患者肿瘤组织和外周血中NF2基因突变,并对其中30例综合采用多重连接依赖探针扩增技术(multiple ligation-dependant probe amplification,MLPA)检测NF2基因大片段缺失.结果标准测序检测听神经瘤组织NF2基因突变率为39.3%,外周血中突变率为零；移码、剪切位点、无义、错义突变比例分别为48.5%、21.2%、24.2%和6.1%,突变分布于第1-15外显子,第8外显子为突变高发外显子(15.2%).氨基端、链接区、α-螺旋结构区、羧基端突变分别占总突变率的63.6%、6.1%、21.2%和6.1%.MLPA检测发现NF2基因大片段缺失达73.3%,以氨基端为主(56.7%).标准测序法结合MLPA法测得NF2基因大片段和突变率累计达80.0%.结论散发型听神经瘤中NF2基因突变和大片段缺失率高,且均为体细胞突变.采用标准测序和MLPA结合技术,有助于提高NF2基因突变检出率和精确性.%Objective To study NF2 gene mutations in acoustic neuroma. Methods Tumor tissue and blood samples from 84 patients with acoustic neuroma undergone surgery from January 2007 to December 2010 were collected in this study. Standard sequencing was used to detect NF2 gene mutation. Furthermore, multiple ligation-dependant probe amplifi⁃cation (MLPA) was performed on 30 patients to detect large deletions in the NF2 gene. Results NF2 gene mutation rate on standard sequencing was 39.3%among tumor specimens, but zero in blood samples. The rate of frame shift, splice site, non⁃sense and missence mutation was 48.5%, 21.2%, 24.2%and 6.1%, respectively. NF2 gene mutations occurred between ex⁃on 1 and 15. The exon 8 was the most favorite exon of mutations (15.2%). The rate of mutation in amino terminus, joinning region,α-helical structure and carboxyl terminus were 63.6%, 6.1%, 21.2%and 6.1%, respectively. Large deletions were detected in 73.3%of the patients via MLPA, of which 56.7%were located in amino terminus. The rate of NF2 gene muta⁃tion or large deletion detection increased to 80.0%when MLPA and standard sequencing were combined. Conclusions So⁃matic NF2 mutations and large deletions in the NF2 gene are frequent in sporadic acoustic neuroma. Combined MLPA and standard sequencing improves efficacy of NF2 gene mutation screening.