Pilocytic astrocytoma of the optic pathway: a tumour deriving from radial glia cells with a specific gene signature

Tchoghandjian, Aurélie; Fernandez, Carla; Colin, Carole; Ayachi, Ikbale El; Voutsinos-Porche, Brigitte; Fina, Frédéric; Scavarda, Didier; Piercecchi-Marti, Marie-Dominique; Intagliata, Dominique; Ouafik, L’Houcine; Fraslon-Vanhulle, Caroline; Figarella‐Branger, Dominique

doi:10.1093/brain/awp048

Cited by 59 publications

(50 citation statements)

References 32 publications

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Section: Discussionmentioning

confidence: 99%

“…Prior studies have identified unique gene and protein expression in pathologically similar tumors located at various geographic locations [9, 11]. Many of these proteins are involved in regional brain maturation and may reflect a developmental origin for these tumors [9]. Other studies have identified specific high-risk histologic findings associated with worse outcome in patients with pilocytic astrocytomas, and that these features were unevenly distributed by region of tumor origin [10].…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…These are low-grade lesions with benign histology and are associated with an excellent prognosis after resection [1-8]. While located most commonly in the posterior fossa, this tumor also arises in other characteristic locations within the central nervous system [5, 7-9]. Recent studies have suggested that the histologic and molecular profiles of this tumor type vary with its location of origin [9-11].…”

Section: Introductionmentioning

confidence: 99%

“…While located most commonly in the posterior fossa, this tumor also arises in other characteristic locations within the central nervous system [5, 7-9]. Recent studies have suggested that the histologic and molecular profiles of this tumor type vary with its location of origin [9-11]. While cell proliferation measured by Ki-67 indices has been found to correlate to differing grades of tumor, detailed comparisons within a single pathological diagnosis have not been previously reported [12, 13-16].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence

et al. 2018

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Childhood pilocytic astrocytomas (PA) are low‐grade tumours with an excellent prognosis. However, a minority, particularly those in surgically inaccessible locations, have poorer long‐term outcome. At present, it is unclear whether anatomical location in isolation, or in combination with underlying biological variation, determines clinical behaviour. Here, we have tested the utility of DNA methylation profiling to inform tumour biology and to predict behaviour in paediatric PA. Genome‐wide DNA methylation profiles were generated for 117 paediatric PAs. Using a combination of analyses, we identified DNA methylation variants specific to tumour location and predictive of behaviour. Receiver‐operating characteristic analysis was used to test the predictive utility of clinical and/or DNA methylation features to classify tumour behaviour at diagnosis. Unsupervised analysis distinguished three methylation clusters associated with tumour location (cortical, midline and infratentorial). Differential methylation of 5404 sites identified enrichment of genes involved in ‘embryonic nervous system development’. Specific hypermethylation of NEUROG1 and NR2E1 was identified as a feature of cortical tumours. A highly accurate method to classify tumours according to behaviour, which combined three clinical features (age, location and extent of resection) and methylation level at a single site, was identified. Our findings show location‐specific epigenetic profiles for PAs, potentially reflecting their cell type of origin. This may account for differences in clinical behaviour according to location independent of histopathology. We also defined an accurate method to predict tumour behaviour at diagnosis. This warrants further testing in similar patient cohorts.

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Glioma and Other Neuroepithelial Neoplasms

Palka¹,

Mobley²,

Perkins³

et al. 2012

Textbook of Uncommon Cancer

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Pilocytic astrocytoma of the optic pathway: a tumour deriving from radial glia cells with a specific gene signature

Cited by 59 publications

References 32 publications

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

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

Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence

Glioma and Other Neuroepithelial Neoplasms

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