Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them. In order to find target to fight against vestibular schwannoma, we performed an analysis of gene expression by microarrays.
Project description:Cerebrospinal fluid (liquor) samples (N = 44) have been derived from patients with vestibular schwannoma that comprises about 10% of all intracranial tumors. Applying high resolution tandem mass-spectrometry 525 proteins were identified with high confidence (at least 2 peptides per protein, FDR <1%) in the liquor samples. This dataset provides unique information on proteomic composition of vestibular schwannoma liquor samples.
Project description:Vestibular Schwannoma (VS) is a benign tumor that arises from the Schwann cells of the VIII vestibulocochlear nerve. They contribute to 6-8% of the brain tumors and 80% of tumors originate from the cerebellopontine angle. Cystic vestibular schwannoma (cVS) represents 10% of vestibular schwannomas and are associated with an unpredictable growth behavior and poor surgical outcomes compared with solid vestibular schwannoma (sVS). Long non-coding RNAs (lncRNAs) belong to the class of non-coding RNAs and are known to regulate gene transcription and involved in chromatin remodeling via various mechanism. Despite accumulating evidence demonstrating the crucial roles of lncRNAs in multiple cancers, their comprehensive identification in cVS disease remains unknown. The objective of the current study was to identify lncRNAs associated with cVS using patient cohorts. Applying next generation sequencing, we performed whole transcriptome sequencing (RNA-seq) analysis and identified lncRNAs differentially expressed between cVS and sVS.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.