Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression

• Published in: Experimental & molecular medicine Vol. 56; no. 4; pp. 975 - 986
• Main Authors: Lee, Yeajina, Chowdhury, Tamrin, Kim, Sojin, Yu, Hyeon Jong, Kim, Kyung-Min, Kang, Ho, Kim, Min-Sung, Kim, Jin Wook, Kim, Yong-Hwy, Ji, So Young, Hwang, Kihwan, Han, Jung Ho, Hwang, Jinha, Yoo, Seong-Keun, Lee, Kyu Sang, Choe, Gheeyoung, Won, Jae-Kyung, Park, Sung-Hye, Lee, Yong Kyu, Shin, Joo Heon, Park, Chul-Kee, Kim, Chae-Yong, Kim, Jong-Il
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2024; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 1-Phosphatidylinositol 3-kinase; 38/39; 45/23; 45/43; 631/67/1922; 631/67/68/2486; AKT protein; Artificial intelligence; Biomedical and Life Sciences; Biomedicine; Brain cancer; Brain diseases; Brain tumors; Cell differentiation; Central nervous system; DNA Methylation; Ependymoglial Cells - metabolism; Ependymoglial Cells - pathology; Fibroblast growth factor receptors; Gene Expression Regulation, Neoplastic; Genomics; Glial cells; Humans; Medical Biochemistry; Molecular Medicine; Neurocytoma - genetics; Neurocytoma - metabolism; Neurocytoma - pathology; Neuronal-glial interactions; Ontogeny; Radial glial cells; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Receptor, Fibroblast Growth Factor, Type 3 - metabolism; Stem Cells; Tumor cells; Tumorigenesis; Young adults; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-024-01204-3

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN. Genomic breakthrough: FGFR3 overexpression drives rare brain tumor Central neurocytoma (CN, a rare brain tumor usually found in young adults) is not well understood due to its rarity. This study used advanced technology to analyze the genetic makeup of CN. The researchers found that CNs don't have any major repeated changes in their genes, gene combinations, or gene copies that could cause the tumor. Instead, they found that the increase in activity of the PI3K-AKT pathway (a pathway involved in cell growth) and changes in several pathways involved in nerve cell development are controlled by an increase in FGFR3 (a protein that helps cells grow and divide) in CNs. This research provides important information about the genetics of CN and could help guide future research and treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author. Introduction