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Molecular profiling of rhabdoid tumors in a Smarcb1-deficient mouse model

ABSTRACT: Germline mutations of the SMARCB1 gene predispose to two distinct tumor syndromes: rhabdoid tumor predisposition syndrome, with malignant pediatric tumors mostly developing in brain and kidney, and familial schwannomatosis, with adulthood benign tumors involving cranial and peripheral nerves. The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus schwannomas are still unknown. Here, to understand the origin of these two types of SMARCB1-associated tumors, we generated different tissue- and developmental stage-specific conditional knockout mice carrying Smarcb1 and/or Nf2 deletion. Smarcb1 loss in early neural crest was necessary to initiate tumorigenesis in the cranial nerves and meninges with typical histological features and molecular profiles of human rhabdoid tumors. By inducing Smarcb1 loss at later developmental stage in the Schwann cell lineage, in addition to biallelic Nf2 gene inactivation, we generated the first mouse model developing schwannomas with the same underlying gene mutations found in schwannomatosis patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE94082 | GEO | 2017/10/31

SECONDARY ACCESSION(S): PRJNA368806

REPOSITORIES: GEO

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Global Profiling in Vestibular Schwannomas Shows Critical Deregulation of MicroRNAs and Upregulation in those included in Chromosomal Region 14q32

Project description:Background: Vestibular Schwannomas are benign tumors that arise from Schwann cells in the VIII cranial pair and usually present NF2 gene mutations and/or loss of heterozygosity on chromosome 22q. Deregulation has also been found in several genes, such as ERBB2 and NRG1. MicroRNAs are non-coding RNAs approximately 21 to 23 nucleotides in length that regulate mRNAs, usually by degradation at the post-transcriptional level. Methods: We used microarray technology to test the deregulation of miRNAs and other non-coding RNAs present in GeneChip miRNA 1.0 (Affymetrix) over 16 vestibular Schwannomas and 3 control-nerves, validating 10 of them by qRT-PCR. Findings: Our results showed the deregulation of 174 miRNAs, including miR-10b, miR-206, miR-183 and miR-204, and the upregulation of miR-431, miR-221, miR-21 and miR-720, among others. The results also showed an aberrant expression of other non-coding RNAs. We also found a general upregulation of the miRNA cluster located at chromosome 14q32. Conclusion: Our results suggest that several miRNAs are involved in tumor formation and/or maintenance and that global upregulation of the 14q32 chromosomal site may represent a therapeutic target for this neoplasm. 16 Vestibular Schwannomas and 3 control-nerves were analysed

2014-03-24 | E-GEOD-43571 | biostudies-arrayexpress

Chip of BRD4 in Neurofibromatosis type 2

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2022-08-02 | GSE167560 | GEO

Microarray Analysis in Vestibular Schwannomas

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2013-03-01 | E-GEOD-39645 | biostudies-arrayexpress

Global expression profile in a combined study in low grade meningiomas and schwannomas shows upregulation in PDGF, CDH1, SLIT2 and MET.

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2013-03-01 | GSE39645 | GEO

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2013-12-31 | E-GEOD-46017 | biostudies-arrayexpress

Treatment of Novel Patient-Derived Xenograft and Cell Line Models with PI3K/AKT/mTOR Inhibitors Revealed Treatment Response Heterogeneity in NF2-Associated Schwannoma

Project description:Treatment of multiple intracranial schwannomas in patient with neurofibromatosis type 2 (NF2) is extremely unsatisfactory and innovative therapeutic approaches are urgently needed. The lack of clinically relevant NF2 models has severely hampered drug discovery in this rare disease. Here, we report for the first time the establishment and characterization of patient-derived xenograft (PDX) and cell line models of NF2-associated schwannoma, which retain the gene mutations and transcriptome profile, and recapitulate the morphological and histopathological features with the patient tumors, retain patient NF2 mutations, and maintain gene expression profiles resembling the patient tumor profiles with the preservation of multiple key signaling pathways commonly dysregulated in human schwannoma. Using expression profiling, we found that the PI3K/AKT/mTOR networks are elevated in NF2-associated vestibular schwannomas, as well as in PDX models.

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2014-03-24 | GSE43571 | GEO

RNA sequencing data from primary atypical teratoid rhabdoid tumor (ATRT) samples

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2020-12-18 | GSE160748 | GEO

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