Functional relevance of genes predicted to be affected by epigenetic alterations in atypical teratoid/rhabdoid tumors

Tegeder, Isabel; Thiel, Katharina; Erkek, Serap; Johann, Pascal; Berlandi, Johannes; Thatikonda, Venu; Frühwald, Michael C.; Kool, Marcel; Jeibmann, Astrid; Hasselblatt, Martin

doi:10.1007/s11060-018-03018-6

Cited by 10 publications

(7 citation statements)

References 40 publications

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“…We found Snr1 is needed for the transition from neuroepithelial cells into neuroblasts, as well as for neuroblast differentiation. These transitions are regulated by multiple pathways ( Apitz and Salecker, 2014 ), and Snr1 has been shown to regulate the expression of a large number of genes ( Tegeder et al, 2019 ). Comparative single cell RNA-sequencing (scRNA-seq) of the entire Drosophila central brain and optic lobes was used to identify the likely targets of Snr1 that are important for guiding these transitions ( Fig.…”

Section: Resultsmentioning

confidence: 99%

A chromatin remodelling SWI/SNF subunit, Snr1, regulates neural stem cell determination and differentiation

et al. 2023

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Coordinated spatio-temporal regulation of the determination and differentiation of neural stem cells is essential for brain development. Failure to integrate multiple factors leads to defective brain structures or tumor formation. Previous studies suggest changes of chromatin state are needed to direct neural stem cell differentiation, but the mechanisms are unclear. Analysis of Snr1, the Drosophila orthologue of SMARCB1, an ATP-dependent chromatin remodelling protein, identified a key role in regulating the transition of neuroepithelial cells into neural stem cells and subsequent differentiation of neural stem cells into cells needed to build the brain. Loss of Snr1 in neuroepithelial cells leads to premature neural stem cell formation. Additionally, loss of Snr1 in neural stem cells results in inappropriate perdurance of neural stem cells into adulthood. Snr1 reduction in neuroepithelial or neural stem cells leads to the differential expression of target genes. We find that Snr1 is associated with the actively transcribed chromatin region of these target genes. Thus, Snr1 likely regulates the chromatin state in neuroepithelial cells and maintains chromatin state in neural stem cells for proper brain development.

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Section: Resultsmentioning

confidence: 99%

A chromatin remodelling SWI/SNF subunit, Snr1, regulates neural stem cell determination and differentiation

et al. 2023

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“…Hu et al [43] reported that PRDM16 transforming megakaryocyte-erythroid progenitors into myeloid leukemia stem cells. In another study, PRDM16 knockdown induced cell proliferation in rhabdoid tumor cells [44], suggesting that PRDM16 may be an oncogene in leukemia development, although in other tumor types PRDM16 has a controversial role [45,46]. Thus, the role of PRDM16 in cancer biology has been poorly studied and remains to be fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Identifying novel genetic alterations in pediatric acute lymphoblastic leukemia based on copy number analysis

et al. 2020

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Copy number variations (CNVs) analysis may reveal molecular biomarkers and provide information on the pathogenesis of acute lymphoblastic leukemia (ALL). We investigated the gene copy number in childhood ALL by microarray and select three new recurrent CNVs to evaluate by real-time PCR assay: DMBT1, KIAA0125 and PRDM16 were selected due to high frequency of CNVs in ALL samples and based on their potential biological functions in carcinogenesis described in the literature. DBMT1 deletion was associated with patients with chromosomal translocations and is a potential tumor suppressor; KIAA0125 and PRDM16 may act as an oncogene despite having a paradoxical behavior in carcinogenesis. This study reinforces that microarrays/aCGH is it is a powerful tool for detection of genomic aberrations, which may be used in the risk stratification.

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“…Weighted gene expression network analysis has defined PRDM16 among the hub genes in renal cell carcinoma with an effect on patient survival suggesting it might be considered as a novel candidate biomarker of this malignancy [260]. Additionally, PRDM16 is highly overexpressed also in atypical teratoid/rhabdoid tumor, a highly malignant brain tumor predominantly arising in infants; moreover, it could have a functional role in human rhabdoid tumor cells since PRDM16 knockdown resulted in reduced metabolic activity and proliferation [261]. A different approach identified PRDM16 as a possible therapeutic target in PC.…”

Section: Prdm16mentioning

confidence: 99%

Multifaceted Role of PRDM Proteins in Human Cancer

Casamassimi

Rienzo

Zazzo

et al. 2020

IJMS

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The PR/SET domain family (PRDM) comprise a family of genes whose protein products share a conserved N-terminal PR [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1)] homologous domain structurally and functionally similar to the catalytic SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain of histone methyltransferases (HMTs). These genes are involved in epigenetic regulation of gene expression through their intrinsic HMTase activity or via interactions with other chromatin modifying enzymes. In this way they control a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, and maintenance of immune cell homeostasis. In cancer, tumor-specific dysfunctions of PRDM genes alter their expression by genetic and/or epigenetic modifications. A common characteristic of most PRDM genes is to encode for two main molecular variants with or without the PR domain. They are generated by either alternative splicing or alternative use of different promoters and play opposite roles, particularly in cancer where their imbalance can be often observed. In this scenario, PRDM proteins are involved in cancer onset, invasion, and metastasis and their altered expression is related to poor prognosis and clinical outcome. These functions strongly suggest their potential use in cancer management as diagnostic or prognostic tools and as new targets of therapeutic intervention.

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Functional relevance of genes predicted to be affected by epigenetic alterations in atypical teratoid/rhabdoid tumors

Cited by 10 publications

References 40 publications

A chromatin remodelling SWI/SNF subunit, Snr1, regulates neural stem cell determination and differentiation

A chromatin remodelling SWI/SNF subunit, Snr1, regulates neural stem cell determination and differentiation

Identifying novel genetic alterations in pediatric acute lymphoblastic leukemia based on copy number analysis

Multifaceted Role of PRDM Proteins in Human Cancer

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