genetic and epigenetic alterations of the nf2 gene in sporadic vestibular schwannomasnf2基因的遗传和表观遗传改变在零星的前庭神经鞘瘤.pdfVIP

Genetic and Epigenetic Alterations of the NF2 Gene in Sporadic Vestibular Schwannomas 1. 2. 2 3 Jong Dae Lee , Tae Jun Kwon , Un-Kyung Kim *, Won-Sang Lee 1 Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Korea, 2 Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Korea, 3 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea Abstract Background: Mutations in the neurofibromatosis type 2 (NF2) tumor-suppressor gene have been identified in not only NF2- related tumors but also sporadic vestibular schwannomas (VS). This study investigated the genetic and epigenetic alterations in tumors and blood from 30 Korean patients with sporadic VS and correlated these alterations with tumor behavior. Methodology/Principal Findings: NF2 gene mutations were detected using PCR and direct DNA sequencing and three highly polymorphic microsatellite DNA markers were used to assess the loss of heterozygosity (LOH) from chromosome 22. Aberrant hypermethylation of the CpG island of the NF2 gene was also analyzed. The tumor size, the clinical growth index, and the proliferative activity assessed using the Ki-67 labeling index were evaluated. We found 18 mutations in 16 cases of 30 schwannomas (53%). The mutations included eight frameshift mutations, seven nonsense mutations, one in-frame deletion, one splicing donor site, and one missense mutation. Nine patients (30%) showed allelic loss. No patient had aberrant hypermethylation of the NF2 gene and correlation between NF2 genetic alterations and tumor behavior was not observed in this study.