Comprehensive multiomics analysis reveals distinct differences between pediatric choroid plexus papilloma and carcinoma.
Choroid plexus tumor
Methylation sequencing
Multiomics
Whole-genome sequencing
Whole-transcriptome sequencing
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
12 Jun 2024
12 Jun 2024
Historique:
received:
08
02
2024
accepted:
02
06
2024
medline:
13
6
2024
pubmed:
13
6
2024
entrez:
12
6
2024
Statut:
epublish
Résumé
Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC. Multiomics analysis included whole-genome sequencing, whole-transcriptome sequencing, and methylation sequencing. Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP. Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP. Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination. Furthermore, methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC. Finally, the differential expression of AK1, regulated by both genomic and epigenomic factors, emerged as a potential contributing factor to the histological difference of CPP against CPC. Our results suggest pronounced genomic and epigenomic disparities between CPP and CPC, providing insights into the pathogenesis of CPT at the molecular level.
Identifiants
pubmed: 38867333
doi: 10.1186/s40478-024-01814-y
pii: 10.1186/s40478-024-01814-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
93Subventions
Organisme : Seoul National University Hospital Research Fund
ID : 03-20220260
Organisme : SNUH Kun-hee Lee Child Cancer & Rare Disease Project
ID : 70-20221202
Organisme : Ulsan 10K Genomes Project
ID : 1.180017.01
Organisme : National Research Foundation of Korea
ID : NRF-2021R1A6A3A13045998
Organisme : National Research Foundation of Korea
ID : NRF-2018R1A6A1A03025810
Informations de copyright
© 2024. The Author(s).
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