关键词：遗传学；肿瘤发生；障碍；血液
摘 要：About half of schwannomas are driven by loss of the NF2 tumor suppressor gene; however, a major barrier to more effective therapies is the lack of a comprehensive understanding of the genetic events outside of the NF2 gene in these tumors. In this project, we hypothesized that additional point mutations, copy-number changes, and fusion events between distant regions of the genome, drive the development of these tumors. To address this hypothesis, we have obtained schwannoma tissue and matched blood and begun examining the somatic genetic alterations through next-generation sequencing. To date, five pairs have undergone exome sequencing, while two additional samples are undergoing whole-genome sequencing. Many additional samples from new collaborators are scheduled for additional sequencing. Interestingly, among the five whole-exome sequenced schwannoma samples, the mutation rates are low, with three of the five samples harboring NF2 mutations. Additionally, we have identified a mutation in the proto-oncogene CBL in one sample and a genomic translocation disrupting RB1 in another sample, though both of these findings will require further validation. These findings begin to shed some light on the molecular complexity of schwannoma formation, and analysis of additional samples will greatly assist in our efforts.