| Autor: |
Nomura, Masashi, Saito, Kuniaki, Aihara, Koki, Nagae, Genta, Yamamoto, Shogo, Tatsuno, Kenji, Ueda, Hiroki, Fukuda, Shiro, Umeda, Takayoshi, Tanaka, Shota, Takayanagi, Shunsaku, Otani, Ryohei, Nejo, Takahide, Hana, Taijun, Takahashi, Satoshi, Kitagawa, Yosuke, Omata, Mayu, Higuchi, Fumi, Nakamura, Taishi, Muragaki, Yoshihiro |
| Zdroj: |
Scientific Reports; 2/13/2019, Vol. 9 Issue 1, p1-1, 1p |
| Abstrakt: |
To elucidate the mechanisms of malignant progression of lower-grade glioma, molecular profiling using methylation array, whole-exome sequencing, and RNA sequencing was performed for 122, 36 and 31 gliomas, respectively. This cohort included 24 matched pairs of initial lower-grade gliomas and recurrent tumors, most of which showed malignant progression. Nearly half of IDH-mutant glioblastomas that had progressed from lower-grade gliomas exhibited characteristic partial DNA demethylation in previously methylated genomic regions of their corresponding initial tumors, which had the glioma CpG island methylator phenotype (G-CIMP). In these glioblastomas, cell cycle-related genes, RB and PI3K-AKT pathway genes were frequently altered. Notably, late-replicating domain was significantly enriched in the demethylated regions that were mostly located in non-regulatory regions, suggesting that the loss of DNA methylation during malignant transformation may involve mainly passive demethylation due to a delay in maintenance of methylation during accelerated cell division. Nonetheless, a limited number of genes including IGF2BP3, which potentially drives cell proliferation, were presumed to be upregulated due to demethylation of their promoter. Our data indicated that demethylation of the G-CIMP profile found in a subset of recurrent gliomas reflects accelerated cell divisions accompanied by malignant transformation. Oncogenic genes activated by such epigenetic change represent potential therapeutic targets. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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