Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses
Abstract Nowadays medulloblastoma (MB) tumors can be treated with risk-stratified approaches with up to 80% success rate. However, disease relapses occur in approximately 30% of patients and successful salvage treatment strategies at relapse remain scarce. Acquired copy number changes or TP53 mutati...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-023-01504-1 |
| _version_ | 1797952256471990272 |
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| author | Konstantin Okonechnikov Aniello Federico Daniel Schrimpf Philipp Sievers Felix Sahm Jan Koster David T. W. Jones Andreas von Deimling Stefan M. Pfister Marcel Kool Andrey Korshunov |
| author_facet | Konstantin Okonechnikov Aniello Federico Daniel Schrimpf Philipp Sievers Felix Sahm Jan Koster David T. W. Jones Andreas von Deimling Stefan M. Pfister Marcel Kool Andrey Korshunov |
| author_sort | Konstantin Okonechnikov |
| collection | DOAJ |
| description | Abstract Nowadays medulloblastoma (MB) tumors can be treated with risk-stratified approaches with up to 80% success rate. However, disease relapses occur in approximately 30% of patients and successful salvage treatment strategies at relapse remain scarce. Acquired copy number changes or TP53 mutations are known to occur frequently in relapses, while methylation profiles usually remain highly similar to those of the matching primary tumors, indicating that in general molecular subgrouping does not change during the course of the disease. In the current study, we have used RNA sequencing data to analyze the transcriptome profiles of 43 primary-relapse MB pairs in order to identify specific molecular features of relapses within various tumor groups. Gene variance analysis between primary and relapse samples demonstrated the impact of age in SHH-MB: the changes in gene expression relapse profiles were more pronounced in the younger patients (< 10 years old), which were also associated with increased DNA aberrations and somatic mutations at relapse probably driving this effect. For Group 3/4 MB transcriptome data analysis uncovered clear sets of genes either active or decreased at relapse that are significantly associated with survival, thus could be potential predictive markers. In addition, deconvolution analysis of bulk transcriptome data identified progression-associated differences in cell type enrichment. The proportion of undifferentiated progenitors increased in SHH-MB relapses with a concomitant decrease of differentiated neuron-like cells, while in Group 3/4 MB relapses cell cycle activity increases and differentiated neuron-like cells proportion decreases as well. Thus, our findings uncovered significant transcriptome changes in the molecular signatures of relapsed MB and could be potentially useful for further clinical purposes. |
| first_indexed | 2024-04-10T22:44:29Z |
| format | Article |
| id | doaj.art-0289bf3c012b4571ab30fae8f9253fa0 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-10T22:44:29Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-0289bf3c012b4571ab30fae8f9253fa02023-01-15T12:24:02ZengBMCActa Neuropathologica Communications2051-59602023-01-0111111210.1186/s40478-023-01504-1Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapsesKonstantin Okonechnikov0Aniello Federico1Daniel Schrimpf2Philipp Sievers3Felix Sahm4Jan Koster5David T. W. Jones6Andreas von Deimling7Stefan M. Pfister8Marcel Kool9Andrey Korshunov10Hopp Children’s Cancer Center Heidelberg (KiTZ)Hopp Children’s Cancer Center Heidelberg (KiTZ)Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)Hopp Children’s Cancer Center Heidelberg (KiTZ)Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam and Cancer Center AmsterdamHopp Children’s Cancer Center Heidelberg (KiTZ)Hopp Children’s Cancer Center Heidelberg (KiTZ)Hopp Children’s Cancer Center Heidelberg (KiTZ)Hopp Children’s Cancer Center Heidelberg (KiTZ)Hopp Children’s Cancer Center Heidelberg (KiTZ)Abstract Nowadays medulloblastoma (MB) tumors can be treated with risk-stratified approaches with up to 80% success rate. However, disease relapses occur in approximately 30% of patients and successful salvage treatment strategies at relapse remain scarce. Acquired copy number changes or TP53 mutations are known to occur frequently in relapses, while methylation profiles usually remain highly similar to those of the matching primary tumors, indicating that in general molecular subgrouping does not change during the course of the disease. In the current study, we have used RNA sequencing data to analyze the transcriptome profiles of 43 primary-relapse MB pairs in order to identify specific molecular features of relapses within various tumor groups. Gene variance analysis between primary and relapse samples demonstrated the impact of age in SHH-MB: the changes in gene expression relapse profiles were more pronounced in the younger patients (< 10 years old), which were also associated with increased DNA aberrations and somatic mutations at relapse probably driving this effect. For Group 3/4 MB transcriptome data analysis uncovered clear sets of genes either active or decreased at relapse that are significantly associated with survival, thus could be potential predictive markers. In addition, deconvolution analysis of bulk transcriptome data identified progression-associated differences in cell type enrichment. The proportion of undifferentiated progenitors increased in SHH-MB relapses with a concomitant decrease of differentiated neuron-like cells, while in Group 3/4 MB relapses cell cycle activity increases and differentiated neuron-like cells proportion decreases as well. Thus, our findings uncovered significant transcriptome changes in the molecular signatures of relapsed MB and could be potentially useful for further clinical purposes.https://doi.org/10.1186/s40478-023-01504-1MedulloblastomaRelapsesTranscriptomicsPrognosis |
| spellingShingle | Konstantin Okonechnikov Aniello Federico Daniel Schrimpf Philipp Sievers Felix Sahm Jan Koster David T. W. Jones Andreas von Deimling Stefan M. Pfister Marcel Kool Andrey Korshunov Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses Acta Neuropathologica Communications Medulloblastoma Relapses Transcriptomics Prognosis |
| title | Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses |
| title_full | Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses |
| title_fullStr | Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses |
| title_full_unstemmed | Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses |
| title_short | Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses |
| title_sort | comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses |
| topic | Medulloblastoma Relapses Transcriptomics Prognosis |
| url | https://doi.org/10.1186/s40478-023-01504-1 |
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