Pediatric gliomas as neurodevelopmental disorders

Baker, Suzanne J.; Ellison, David W.; Gutmann, David H.

doi:10.1002/glia.22945

Cited by 59 publications

(51 citation statements)

References 153 publications

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“…Integrated molecular profiling has revolutionized the study of diffusely infiltrating high-grade glial tumors in children, providing evidence for unique mechanisms of molecular pathogenesis reflecting their distinct developmental origins (Baker et al., 2015, Jones and Baker, 2014). Although they are relatively rare, the present study accumulates 1,067 unique cases, a number similar to the aggregated analysis of the The Cancer Genome Atlas adult LGG/GBM cohorts (n = 1122, with grade III included in the “lower-grade” series) (Ceccarelli et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma

et al. 2017

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SummaryWe collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.

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Section: Discussionmentioning

confidence: 99%

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma

et al. 2017

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“…The importance of the PI3K/AKT/mTOR pathway that emerged from our microRNA pathway analysis was not surprising. Along with the MAPK/ERK axis, it is one of the pathways most frequently upregulated in cancers, including pLGGs . Aberrant activation of PI3K/AKT/mTOR signalling in pLGGs has been reported in association with several genetic alterations, including BRAF fusions, FGFR1 duplications, and MYB rearrangements , which are present at different frequencies in the various pLGGs histologies, with the last two genetic alterations that have been more specifically detected in DNET and AG, respectively.…”

Section: Discussionmentioning

confidence: 99%

The miR‐139‐5p regulates proliferation of supratentorial paediatric low‐grade gliomas by targeting the PI3K/AKT/mTORC1 signalling

Catanzaro

Besharat

Miele

et al. 2018

Neuropathology Appl Neurobio

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“…We surmise that tumors with a faster rate of growth may present earlier after formation, presuming that many of these tumors are developmental in origin [9, 17]. Further investigation is required to better understand this observation.…”

Section: Discussionmentioning

confidence: 99%

Proliferative Index in Pediatric Pilocytic Astrocytoma by Region of Origin and Prediction of Clinical Behavior

Robison

Melamed

et al. 2018

Pediatr Neurosurg

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Background/Aims: Pilocytic astrocytomas are common pediatric tumors. Molecular profiles vary with location of origin. Comparisons of proliferation have not been reported. We sought to identify differences in growth by region and whether these predict clinical behavior. Methods: A retrospective review of all patients undergoing surgery for a pilocytic astrocytoma at Children’s Hospital LA from 2003 to 2015 was completed. Tumor location, determined by imaging, was stratified into infratentorial, supratentorial, or optic pathway. Proliferation was measured by Ki-67 immunostaining. A p value of 0.05 was deemed significant. Results: 77 patients were identified. 51 had posterior fossa tumors, 12 had supratentorial tumors, and 14 had optic pathway tumors. Mean Ki-67 score was 3.67, 4.09, and 3.83%, respectively (p = 0.82). Ki-67 of ≥4% trended towards recurrence (p = 0.11), incomplete resection (p = 0.15), and younger age at presentation (p = 0.04). Ki-67 was weakly correlated with shorter survival after surgery (r = –0.103, p = 0.41). Partial resection strongest predicted recurrence (p < 0.001; OR = 13.0). Conclusion: Proliferative index does not change by location. Higher cell proliferation was seen in younger patients and associated with shorter time to and a higher risk of recurrence. Further study is needed to identify predictors for clinical behavior. Importance of Study: This study provides a detailed analysis of the proliferative indices of tumors arising from characteristic locations within the brain. With recent advances in our understanding of the differences in molecular and genetic profiles despite similar histologic diagnoses, we felt that it was important to review whether there were unique components of tumor behavior that could be identified. In turn, we sought to determine whether tumor behavior could be used to predict the clinical course. This knowledge is important, given that not every tumor may undergo complete surgical resection, and that some lesions may require more aggressive upfront adjuvant therapy or be closely monitored for recurrence.

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Pediatric gliomas as neurodevelopmental disorders

Cited by 59 publications

References 153 publications

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma

The miR‐139‐5p regulates proliferation of supratentorial paediatric low‐grade gliomas by targeting the PI3K/AKT/mTORC1 signalling

Proliferative Index in Pediatric Pilocytic Astrocytoma by Region of Origin and Prediction of Clinical Behavior

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