DNA methylation alterations across time and space in paediatric brain tumours
Abstract DNA methylation is increasingly used for tumour classification and has expanded upon the > 100 currently known brain tumour entities. A correct diagnosis is the basis for suitable treatment for patients with brain tumours, which is the leading cause of cancer-related death in children. D...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-07-01
|
| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-022-01406-8 |
| _version_ | 1828541658676854784 |
|---|---|
| author | Anna Wenger Sandra Ferreyra Vega Elizabeth Schepke Maja Löfgren Thomas Olsson Bontell Magnus Tisell Daniel Nilsson Teresia Kling Helena Carén |
| author_facet | Anna Wenger Sandra Ferreyra Vega Elizabeth Schepke Maja Löfgren Thomas Olsson Bontell Magnus Tisell Daniel Nilsson Teresia Kling Helena Carén |
| author_sort | Anna Wenger |
| collection | DOAJ |
| description | Abstract DNA methylation is increasingly used for tumour classification and has expanded upon the > 100 currently known brain tumour entities. A correct diagnosis is the basis for suitable treatment for patients with brain tumours, which is the leading cause of cancer-related death in children. DNA methylation profiling is required for diagnosis of certain tumours, and used clinically for paediatric brain tumours in several countries. We therefore evaluated if the methylation-based classification is robust in different locations of the same tumour, and determined how the methylation pattern changed over time to relapse. We sampled 3–7 spatially separated biopsies per patient, and collected samples from paired primary and relapse brain tumours from children. Altogether, 121 samples from 46 paediatric patients with brain tumours were profiled with EPIC methylation arrays. The methylation-based classification was mainly homogeneous for all included tumour types that were successfully classified, which is promising for clinical diagnostics. There were indications of multiple subclasses within tumours and switches in the relapse setting, but not confirmed as the classification scores were below the threshold. Site-specific methylation alterations did occur within the tumours and varied significantly between tumour types for the temporal samples, and as a trend in spatial samples. More alterations were present in high-grade tumours compared to low-grade, and significantly more alterations with longer relapse times. The alterations in the spatial and temporal samples were significantly depleted in CpG islands, exons and transcription start sites, while enriched in OpenSea and regions not affiliated with a gene, suggesting a random location of the alterations in less conserved regions. In conclusion, more DNA methylation changes accumulated over time and more alterations occurred in high-grade tumours. The alterations mainly occurred in regions without gene affiliation, and did not affect the methylation-based classification, which largely remained homogeneous in paediatric brain tumours. |
| first_indexed | 2024-12-12T01:43:04Z |
| format | Article |
| id | doaj.art-314bf8a820aa4c669a7178991cf1a55a |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-12T01:43:04Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-314bf8a820aa4c669a7178991cf1a55a2022-12-22T00:42:38ZengBMCActa Neuropathologica Communications2051-59602022-07-0110111410.1186/s40478-022-01406-8DNA methylation alterations across time and space in paediatric brain tumoursAnna Wenger0Sandra Ferreyra Vega1Elizabeth Schepke2Maja Löfgren3Thomas Olsson Bontell4Magnus Tisell5Daniel Nilsson6Teresia Kling7Helena Carén8Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Neurosurgery, Sahlgrenska University HospitalDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgAbstract DNA methylation is increasingly used for tumour classification and has expanded upon the > 100 currently known brain tumour entities. A correct diagnosis is the basis for suitable treatment for patients with brain tumours, which is the leading cause of cancer-related death in children. DNA methylation profiling is required for diagnosis of certain tumours, and used clinically for paediatric brain tumours in several countries. We therefore evaluated if the methylation-based classification is robust in different locations of the same tumour, and determined how the methylation pattern changed over time to relapse. We sampled 3–7 spatially separated biopsies per patient, and collected samples from paired primary and relapse brain tumours from children. Altogether, 121 samples from 46 paediatric patients with brain tumours were profiled with EPIC methylation arrays. The methylation-based classification was mainly homogeneous for all included tumour types that were successfully classified, which is promising for clinical diagnostics. There were indications of multiple subclasses within tumours and switches in the relapse setting, but not confirmed as the classification scores were below the threshold. Site-specific methylation alterations did occur within the tumours and varied significantly between tumour types for the temporal samples, and as a trend in spatial samples. More alterations were present in high-grade tumours compared to low-grade, and significantly more alterations with longer relapse times. The alterations in the spatial and temporal samples were significantly depleted in CpG islands, exons and transcription start sites, while enriched in OpenSea and regions not affiliated with a gene, suggesting a random location of the alterations in less conserved regions. In conclusion, more DNA methylation changes accumulated over time and more alterations occurred in high-grade tumours. The alterations mainly occurred in regions without gene affiliation, and did not affect the methylation-based classification, which largely remained homogeneous in paediatric brain tumours.https://doi.org/10.1186/s40478-022-01406-8Childhood cancerDNA methylationBrain tumourEPIC methylation arrayHeterogeneityIntratumour |
| spellingShingle | Anna Wenger Sandra Ferreyra Vega Elizabeth Schepke Maja Löfgren Thomas Olsson Bontell Magnus Tisell Daniel Nilsson Teresia Kling Helena Carén DNA methylation alterations across time and space in paediatric brain tumours Acta Neuropathologica Communications Childhood cancer DNA methylation Brain tumour EPIC methylation array Heterogeneity Intratumour |
| title | DNA methylation alterations across time and space in paediatric brain tumours |
| title_full | DNA methylation alterations across time and space in paediatric brain tumours |
| title_fullStr | DNA methylation alterations across time and space in paediatric brain tumours |
| title_full_unstemmed | DNA methylation alterations across time and space in paediatric brain tumours |
| title_short | DNA methylation alterations across time and space in paediatric brain tumours |
| title_sort | dna methylation alterations across time and space in paediatric brain tumours |
| topic | Childhood cancer DNA methylation Brain tumour EPIC methylation array Heterogeneity Intratumour |
| url | https://doi.org/10.1186/s40478-022-01406-8 |
| work_keys_str_mv | AT annawenger dnamethylationalterationsacrosstimeandspaceinpaediatricbraintumours AT sandraferreyravega dnamethylationalterationsacrosstimeandspaceinpaediatricbraintumours AT elizabethschepke dnamethylationalterationsacrosstimeandspaceinpaediatricbraintumours AT majalofgren dnamethylationalterationsacrosstimeandspaceinpaediatricbraintumours AT thomasolssonbontell dnamethylationalterationsacrosstimeandspaceinpaediatricbraintumours AT magnustisell dnamethylationalterationsacrosstimeandspaceinpaediatricbraintumours AT danielnilsson dnamethylationalterationsacrosstimeandspaceinpaediatricbraintumours AT teresiakling dnamethylationalterationsacrosstimeandspaceinpaediatricbraintumours AT helenacaren dnamethylationalterationsacrosstimeandspaceinpaediatricbraintumours |