What Genes Can Tell: A Closer Look at Vestibular Schwannoma

作者：Ksenia A. Aaron, Zarko Manojlovic, Nathan Tu, Yili Xu, Yuxin Jin, Sharon B. Chang, Eric S. C. Kwok, Michelle G. Webb, Kyle Hurth, Rick A. Friedman · 发表于：Otology & Neurotology · 年份：2020 · DOI：10.1097/mao.0000000000002580 · 被引用次数：16 · 研究领域：Meningioma and schwannoma management、Neurofibromatosis and Schwannoma Cases、Ear and Head Tumors

OBJECTIVE: Comprehensive molecular profiling of radioresistant and cystic vestibular schwannoma (VS) subtypes. STUDY DESIGN: Our study utilized whole-exome sequencing (WES), RNA-sequencing (RNAseq), and correlated clinical data from 12 samples (2 samples of solid sporadic subtype, 8 with cystic changes, and 2 previously irradiated). SETTING: Academic medical center. PATIENTS: Patients diagnosed with VS who required surgical treatment. Inclusion: Cystic and radioresistant tumors matched to age and tumor volume, with solid sporadic VS samples as control; Exclusion: NF-2 patients. INTERVENTION(S): WES using custom probes for copy number analysis. A modified version of the Agilent Human Whole Exome sequencing hybrid capture system was used to process samples. Recurrent variants were identified and compared between groups. Leukocyte-derived DNA was utilized as internal control to reduce false-positives. MAIN OUTCOME MEASURE(S): Analysis of genetic landscape of VS subtypes (naive solid VS, cystic VS, and previously irradiated VS) by performing deep next-generation sequencing. RESULTS: WES data achieved a mean coverage of 202X and RNAseq generated an average of 74 million total reads. As a group, 25% of samples had 22q loss. Somatic analysis identified previously reported genes and multiple novel mutations across samples. Differential expression analysis of RNAseq data found significantly mutated genes such as COL6A3, CLMP, ART4, Lumican that were shared by both cystic VS and irradi...