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MBRS-69. METABOLITE PROFILING OF SHH MEDULLOBLASTOMA IDENTIFIES A SUBSET OF CHILDHOOD TUMOURS ENRICHED FOR HIGH-RISK MOLECULAR BIOMARKERS AND CLINICAL FEATURES

SHH medulloblastoma patients have a variable prognosis. Infants (<3–5 years at diagnosis) are associated with a good prognosis, while disease-course in childhood is associated with specific prognostic biomarkers (MYCN amplification, TP53 mutation, LCA histology; all high-risk). There is an unmet...

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Autores principales: Bennett, Christopher, Kohe, Sarah, Burte, Florence, Rose, Heather, Hicks, Debbie, Schwalbe, Ed, Crosier, Stephen, Storer, Lisa, Lourdusamy, Anbarasu, Wilson, Martin, Avula, Shivaram, Mitra, Dipayan, Dineen, Robert, Bailey, Simon, Williamson, Daniel, Grundy, Richard, Clifford, Steven, Peet, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715738/
http://dx.doi.org/10.1093/neuonc/noaa222.573
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author Bennett, Christopher
Kohe, Sarah
Burte, Florence
Rose, Heather
Hicks, Debbie
Schwalbe, Ed
Crosier, Stephen
Storer, Lisa
Lourdusamy, Anbarasu
Wilson, Martin
Avula, Shivaram
Mitra, Dipayan
Dineen, Robert
Bailey, Simon
Williamson, Daniel
Grundy, Richard
Clifford, Steven
Peet, Andrew
author_facet Bennett, Christopher
Kohe, Sarah
Burte, Florence
Rose, Heather
Hicks, Debbie
Schwalbe, Ed
Crosier, Stephen
Storer, Lisa
Lourdusamy, Anbarasu
Wilson, Martin
Avula, Shivaram
Mitra, Dipayan
Dineen, Robert
Bailey, Simon
Williamson, Daniel
Grundy, Richard
Clifford, Steven
Peet, Andrew
author_sort Bennett, Christopher
collection PubMed
description SHH medulloblastoma patients have a variable prognosis. Infants (<3–5 years at diagnosis) are associated with a good prognosis, while disease-course in childhood is associated with specific prognostic biomarkers (MYCN amplification, TP53 mutation, LCA histology; all high-risk). There is an unmet need to identify prognostic subgroups of SHH tumours rapidly in the clinical setting, to aid in real-time risk stratification and disease management. Metabolite profiling is a powerful technique for characterising tumours. High resolution magic angle spinning NMR spectroscopy (HR-MAS) can be performed on frozen tissue samples and provides high quality metabolite information. We therefore assessed whether metabolite profiles could identify subsets of SHH tumours with prognostic potential. Metabolite concentrations of 22 SHH tumours were acquired by HR-MAS and analysed using unsupervised hierarchical clustering. Methylation profiling assigned the infant and childhood SHH subtypes, and clinical and molecular features were compared between clusters. Two clusters were observed. A significantly higher concentration of lipids was observed in Cluster 1 (t-test, p=0.012). Cluster 1 consisted entirely of childhood-SHH whilst Cluster 2 included both childhood-SHH and infant-SHH subtypes. Cluster 1 was enriched for high-risk markers - LCA histology (3/7 v. 0/5), MYCN amplification (2/7 v. 0/5), TP53 mutations (3/7 v. 1/5) and metastatic disease - whilst having a lower proportion of TERT mutations (0/7 v. 2/5) than Cluster 2. These pilot results suggest that (i) it is possible to identify childhood-SHH patients linked to high-risk clinical and molecular biomarkers using metabolite profiles and (ii) these may be detected non-invasively in vivo using magnetic-resonance spectroscopy.
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spelling pubmed-77157382020-12-09 MBRS-69. METABOLITE PROFILING OF SHH MEDULLOBLASTOMA IDENTIFIES A SUBSET OF CHILDHOOD TUMOURS ENRICHED FOR HIGH-RISK MOLECULAR BIOMARKERS AND CLINICAL FEATURES Bennett, Christopher Kohe, Sarah Burte, Florence Rose, Heather Hicks, Debbie Schwalbe, Ed Crosier, Stephen Storer, Lisa Lourdusamy, Anbarasu Wilson, Martin Avula, Shivaram Mitra, Dipayan Dineen, Robert Bailey, Simon Williamson, Daniel Grundy, Richard Clifford, Steven Peet, Andrew Neuro Oncol Medulloblastoma (Research) SHH medulloblastoma patients have a variable prognosis. Infants (<3–5 years at diagnosis) are associated with a good prognosis, while disease-course in childhood is associated with specific prognostic biomarkers (MYCN amplification, TP53 mutation, LCA histology; all high-risk). There is an unmet need to identify prognostic subgroups of SHH tumours rapidly in the clinical setting, to aid in real-time risk stratification and disease management. Metabolite profiling is a powerful technique for characterising tumours. High resolution magic angle spinning NMR spectroscopy (HR-MAS) can be performed on frozen tissue samples and provides high quality metabolite information. We therefore assessed whether metabolite profiles could identify subsets of SHH tumours with prognostic potential. Metabolite concentrations of 22 SHH tumours were acquired by HR-MAS and analysed using unsupervised hierarchical clustering. Methylation profiling assigned the infant and childhood SHH subtypes, and clinical and molecular features were compared between clusters. Two clusters were observed. A significantly higher concentration of lipids was observed in Cluster 1 (t-test, p=0.012). Cluster 1 consisted entirely of childhood-SHH whilst Cluster 2 included both childhood-SHH and infant-SHH subtypes. Cluster 1 was enriched for high-risk markers - LCA histology (3/7 v. 0/5), MYCN amplification (2/7 v. 0/5), TP53 mutations (3/7 v. 1/5) and metastatic disease - whilst having a lower proportion of TERT mutations (0/7 v. 2/5) than Cluster 2. These pilot results suggest that (i) it is possible to identify childhood-SHH patients linked to high-risk clinical and molecular biomarkers using metabolite profiles and (ii) these may be detected non-invasively in vivo using magnetic-resonance spectroscopy. Oxford University Press 2020-12-04 /pmc/articles/PMC7715738/ http://dx.doi.org/10.1093/neuonc/noaa222.573 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Medulloblastoma (Research)
Bennett, Christopher
Kohe, Sarah
Burte, Florence
Rose, Heather
Hicks, Debbie
Schwalbe, Ed
Crosier, Stephen
Storer, Lisa
Lourdusamy, Anbarasu
Wilson, Martin
Avula, Shivaram
Mitra, Dipayan
Dineen, Robert
Bailey, Simon
Williamson, Daniel
Grundy, Richard
Clifford, Steven
Peet, Andrew
MBRS-69. METABOLITE PROFILING OF SHH MEDULLOBLASTOMA IDENTIFIES A SUBSET OF CHILDHOOD TUMOURS ENRICHED FOR HIGH-RISK MOLECULAR BIOMARKERS AND CLINICAL FEATURES
title MBRS-69. METABOLITE PROFILING OF SHH MEDULLOBLASTOMA IDENTIFIES A SUBSET OF CHILDHOOD TUMOURS ENRICHED FOR HIGH-RISK MOLECULAR BIOMARKERS AND CLINICAL FEATURES
title_full MBRS-69. METABOLITE PROFILING OF SHH MEDULLOBLASTOMA IDENTIFIES A SUBSET OF CHILDHOOD TUMOURS ENRICHED FOR HIGH-RISK MOLECULAR BIOMARKERS AND CLINICAL FEATURES
title_fullStr MBRS-69. METABOLITE PROFILING OF SHH MEDULLOBLASTOMA IDENTIFIES A SUBSET OF CHILDHOOD TUMOURS ENRICHED FOR HIGH-RISK MOLECULAR BIOMARKERS AND CLINICAL FEATURES
title_full_unstemmed MBRS-69. METABOLITE PROFILING OF SHH MEDULLOBLASTOMA IDENTIFIES A SUBSET OF CHILDHOOD TUMOURS ENRICHED FOR HIGH-RISK MOLECULAR BIOMARKERS AND CLINICAL FEATURES
title_short MBRS-69. METABOLITE PROFILING OF SHH MEDULLOBLASTOMA IDENTIFIES A SUBSET OF CHILDHOOD TUMOURS ENRICHED FOR HIGH-RISK MOLECULAR BIOMARKERS AND CLINICAL FEATURES
title_sort mbrs-69. metabolite profiling of shh medulloblastoma identifies a subset of childhood tumours enriched for high-risk molecular biomarkers and clinical features
topic Medulloblastoma (Research)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715738/
http://dx.doi.org/10.1093/neuonc/noaa222.573
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