Normal and oncogenic roles for microRNAs in the developing brain

Fernández-L, Africa; Northcott, Paul A.; Taylor, Michael D.; Kenney, Anna Marie

doi:10.4161/cc.8.24.10243

Cited by 25 publications

(18 citation statements)

References 43 publications

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“…1). Transcriptional targets of the SHH pathway including the mir17-92 complex, and YAP1 have been demonstrated to be amplified in medulloblastoma where they are acting as oncogenes [27, 28, 77]. Recently, small molecules that inhibit SMO have been demonstrated to be an effective, albeit temporary, therapy for human and mouse medulloblastoma [92, 113].…”

Section: Medulloblastomamentioning

confidence: 99%

Molecular diagnostics of CNS embryonal tumors

et al. 2010

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Tremendous progress has recently been made in both molecular subgrouping, and the establishment of prognostic biomarkers for embryonal brain tumors, particularly medulloblastoma. Several prognostic biomarkers that were initially identified in retrospective cohorts of medulloblastoma, including MYC and MYCN amplification, nuclear β-catenin accumulation, and chromosome 17 aberrations have now been validated in clinical trials. Moreover, molecular subgroups based on distinct transcriptome profiles have been consistently reported from various groups on different platforms demonstrating that the concept of distinct medulloblastoma subgroups is very robust. Well-described subgroups of medulloblastomas include tumors showing wingless signaling pathway (Wnt) activation, and another characterized by sonic hedgehog pathway activity. Two or more additional subgroups were consistently reported to contain the vast majority of high-risk tumors, including most tumors with metastatic disease at diagnosis and/or large cell/anaplastic histology. Several years ago, atypical teratoid rhabdoid tumor (AT/RT) was recognized as a separate entity based on its distinct biology and particularly aggressive clinical behavior. These tumors may occur supra or infratentorially and are usually found to have genetic alterations of SMARCB1 (INI1/hSNF5), a tumor suppressor gene located on chromosome 22q. Subsequent loss of SMARCB1 protein expression comprises a relatively specific and sensitive diagnostic marker for AT/RT. For CNS primitive neuroectodermal tumors (CNS PNETs), a consistent finding has been that they are molecularly distinct from medulloblastoma. Furthermore, a distinct fraction of CNS PNETs with particularly poor prognosis only occurring in young children was delineated, which was previously labeled ependymoblastoma or embryonal tumor with abundant neuropil and true rosettes (ETANTR) and which is morphologically characterized by the presence of multilayered “ependymoblastic” rosettes. This group of tumors shows a unique cytogenetic abnormality not seen in other brain tumors: focal amplification of a micro-RNA cluster at chromosome 19q13.42, which has never been found to be amplified in other CNS PNETs, medulloblastoma or AT/RT. In summary, these consistent findings have significantly contributed to our ability to sub-classify embryonal brain tumors into clinically and biologically meaningful strata and, for some of the subgroups, have led to the identification of specific targets for future development of molecularly targeted therapies.

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Section: Medulloblastomamentioning

confidence: 99%

Molecular diagnostics of CNS embryonal tumors

et al. 2010

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“…40 Different studies using cell lines and human primary tumors highlighted the significance of miRNAs regarding the known genes and signaling pathways involved in medulloblastoma (Table 1). 41,42,47,91,108,118,143,144 MicroRNAs appeared as novel and potential targets for future therapeutics.…”

Section: 85mentioning

confidence: 99%

Epigenetic mechanisms regulating neural development and pediatric brain tumor formation

Faria

Rutka

Smith

et al. 2011

PED

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Pediatric brain tumors are the leading cause of cancer-related death in children, and among them, embryonal tumors represent the largest group with an associated poor prognosis and long-term morbidity for survivors. The field of cancer epigenetics has emerged recently as an important area of investigation and causation of a variety of neoplasms, and is defined as alterations in gene expression without changes in DNA sequence. The best studied epigenetic modifications are DNA methylation, histone modifications, and RNA-based mechanisms. These modifications play an important role in normal development and differentiation but their dysregulation can lead to altered gene function and cancer. In this review the authors describe the mechanisms of normal epigenetic regulation, how they interplay in neuroembryogenesis, and how these can cause brain tumors in children when dysregulated. The potential use of epigenetic markers to design more effective treatment strategies for children with malignant brain tumors is also discussed.

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“…Risk stratification based on clinical parameters is insufficient for accurate prognostication [3]. Current treatment options include surgery, chemotherapy and radiotherapy [4]. However, age limitations for the delivery of radiotherapy have been set due to the vulnerability of the developing brain to radiotherapy-induced neurocognitive deficits [5].…”

Section: Introductionmentioning

confidence: 99%

“…Recent miRNA-based research reveals that a) miRNA profiles of tumor cells are dissimilar from normal cells and b) miRNA expression profiles in tumors from similar developmental origins have similar alterations [10]. Understanding the interplay between normal brain development and CNS tumors pathogenesis is essential for the development and implementation of more efficient and less toxic targeted therapies [4]. Given these, and the fact that miRNAs are less susceptible to chemical modification and RNase degradation, provide the rationale that miRNAs might afford substantial value for neuro-oncology.…”

Section: Introductionmentioning

confidence: 99%

Microrna expression signatures predict patient progression and disease outcome in pediatric embryonal central nervous system neoplasms

et al. 2014

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Background: Although, substantial experimental evidence related to diagnosis and treatment of pediatric central nervous system (CNS) neoplasms have been demonstrated, the understanding of the etiology and pathogenesis of the disease remains scarce. Recent microRNA (miRNA)-based research reveals the involvement of miRNAs in various aspects of CNS development and proposes that they might compose key molecules underlying oncogenesis. The current study evaluated miRNA differential expression detected between pediatric embryonal brain tumors and normal controls to characterize candidate biomarkers related to diagnosis, prognosis and therapy.

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Normal and oncogenic roles for microRNAs in the developing brain

Cited by 25 publications

References 43 publications

Molecular diagnostics of CNS embryonal tumors

Molecular diagnostics of CNS embryonal tumors

Epigenetic mechanisms regulating neural development and pediatric brain tumor formation

Microrna expression signatures predict patient progression and disease outcome in pediatric embryonal central nervous system neoplasms

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