Supratentorial CNS-PNETs in children; a Swedish population-based study with molecular re-evaluation and long-term follow-up
(2023) In Clinical Epigenetics 15(1).- Abstract
Background: Molecular analyses have shown that tumours diagnosed as supratentorial primitive neuro-ectodermal tumours of the central nervous system (CNS-PNETs) in the past represent a heterogenous group of rare childhood tumours including high-grade gliomas (HGG), ependymomas, atypical teratoid/rhabdoid tumours (AT/RT), CNS neuroblastoma with forkhead box R2 (FOXR2) activation and embryonal tumour with multi-layered rosettes (ETMR). All these tumour types are rare and long-term clinical follow-up data are sparse. We retrospectively re-evaluated all children (0–18 years old) diagnosed with a CNS-PNET in Sweden during 1984–2015 and collected clinical data. Methods: In total, 88 supratentorial CNS-PNETs were identified in the Swedish... (More)
Background: Molecular analyses have shown that tumours diagnosed as supratentorial primitive neuro-ectodermal tumours of the central nervous system (CNS-PNETs) in the past represent a heterogenous group of rare childhood tumours including high-grade gliomas (HGG), ependymomas, atypical teratoid/rhabdoid tumours (AT/RT), CNS neuroblastoma with forkhead box R2 (FOXR2) activation and embryonal tumour with multi-layered rosettes (ETMR). All these tumour types are rare and long-term clinical follow-up data are sparse. We retrospectively re-evaluated all children (0–18 years old) diagnosed with a CNS-PNET in Sweden during 1984–2015 and collected clinical data. Methods: In total, 88 supratentorial CNS-PNETs were identified in the Swedish Childhood Cancer Registry and from these formalin-fixed paraffin-embedded tumour material was available for 71 patients. These tumours were histopathologically re-evaluated and, in addition, analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. Results: The most frequent tumour types, after histopathological re-evaluation, were HGG (35%) followed by AT/RT (11%), CNS NB-FOXR2 (10%) and ETMR (8%). DNA methylation profiling could further divide the tumours into specific subtypes and with a high accuracy classify these rare embryonal tumours. The 5 and 10-year overall survival (OS) for the whole CNS-PNET cohort was 45% ± 12% and 42% ± 12%, respectively. However, the different groups of tumour types identified after re-evaluation displayed very variable survival patterns, with a poor outcome for HGG and ETMR patients with 5-year OS 20% ± 16% and 33% ± 35%, respectively. On the contrary, high PFS and OS was observed for patients with CNS NB-FOXR2 (5-year 100% for both). Survival rates remained stable even after 15-years of follow-up. Conclusions: Our findings demonstrate, in a national based setting, the molecular heterogeneity of these tumours and show that DNA methylation profiling of these tumours provides an indispensable tool in distinguishing these rare tumours. Long-term follow-up data confirms previous findings with a favourable outcome for CNS NB-FOXR2 tumours and poor chances of survival for ETMR and HGG.
(Less)
- author
- publishing date
- 2023-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CNS NB-FOXR2, CNS-PNET, DNA methylation profiling, Epigenetics, ETMR, Long term survival
- in
- Clinical Epigenetics
- volume
- 15
- issue
- 1
- article number
- 40
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:36895035
- scopus:85149630750
- ISSN
- 1868-7075
- DOI
- 10.1186/s13148-023-01456-2
- language
- English
- LU publication?
- no
- id
- 5c7fa516-131a-4b53-8bbf-67f728caa61e
- date added to LUP
- 2023-04-21 10:59:53
- date last changed
- 2024-04-19 20:54:44
@article{5c7fa516-131a-4b53-8bbf-67f728caa61e,
abstract = {{<p>Background: Molecular analyses have shown that tumours diagnosed as supratentorial primitive neuro-ectodermal tumours of the central nervous system (CNS-PNETs) in the past represent a heterogenous group of rare childhood tumours including high-grade gliomas (HGG), ependymomas, atypical teratoid/rhabdoid tumours (AT/RT), CNS neuroblastoma with forkhead box R2 (FOXR2) activation and embryonal tumour with multi-layered rosettes (ETMR). All these tumour types are rare and long-term clinical follow-up data are sparse. We retrospectively re-evaluated all children (0–18 years old) diagnosed with a CNS-PNET in Sweden during 1984–2015 and collected clinical data. Methods: In total, 88 supratentorial CNS-PNETs were identified in the Swedish Childhood Cancer Registry and from these formalin-fixed paraffin-embedded tumour material was available for 71 patients. These tumours were histopathologically re-evaluated and, in addition, analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. Results: The most frequent tumour types, after histopathological re-evaluation, were HGG (35%) followed by AT/RT (11%), CNS NB-FOXR2 (10%) and ETMR (8%). DNA methylation profiling could further divide the tumours into specific subtypes and with a high accuracy classify these rare embryonal tumours. The 5 and 10-year overall survival (OS) for the whole CNS-PNET cohort was 45% ± 12% and 42% ± 12%, respectively. However, the different groups of tumour types identified after re-evaluation displayed very variable survival patterns, with a poor outcome for HGG and ETMR patients with 5-year OS 20% ± 16% and 33% ± 35%, respectively. On the contrary, high PFS and OS was observed for patients with CNS NB-FOXR2 (5-year 100% for both). Survival rates remained stable even after 15-years of follow-up. Conclusions: Our findings demonstrate, in a national based setting, the molecular heterogeneity of these tumours and show that DNA methylation profiling of these tumours provides an indispensable tool in distinguishing these rare tumours. Long-term follow-up data confirms previous findings with a favourable outcome for CNS NB-FOXR2 tumours and poor chances of survival for ETMR and HGG.</p>}},
author = {{Schepke, Elizabeth and Löfgren, Maja and Pietsch, Torsten and Kling, Teresia and Nordborg, Claes and Olsson Bontell, Thomas and Holm, Stefan and Öberg, Anders and Nyman, Per and Eliasson-Hofvander, Marie and Sabel, Magnus and Lannering, Birgitta and Carén, Helena}},
issn = {{1868-7075}},
keywords = {{CNS NB-FOXR2; CNS-PNET; DNA methylation profiling; Epigenetics; ETMR; Long term survival}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Clinical Epigenetics}},
title = {{Supratentorial CNS-PNETs in children; a Swedish population-based study with molecular re-evaluation and long-term follow-up}},
url = {{http://dx.doi.org/10.1186/s13148-023-01456-2}},
doi = {{10.1186/s13148-023-01456-2}},
volume = {{15}},
year = {{2023}},
}