ダウンロード数 : ?
言語
英語
著者
Gojo, Johannes
Lotsch, Daniela
Spiegl-Kreinecker, Sabine
Pajtler, Kristian W
Neumayer, Katharina
Korbel, Pia
Brandstetter, Anita
Mohr, Thomas
Hovestadt, Volker
Chavez, Lukas
Kirchhofer, Dominik
Ricken, Gerda
Stefanits, Harald
Korshunov, Andrey
Pfister, Stefan M
Dieckmann, Karin
Azizi, Amedeo A
Czech, Thomas
Filipits, Martin
Kool, Marcel
Peyrl, Andreas
Slavc, Irene
Berger, Walter
Haberler, Christine
内容記述(抄録等)
Background
Ependymomas account for up to 10% of childhood CNS tumors and have a high rate of tumor recurrence despite gross total resection. Recently, classification into molecular ependymoma subgroups has been established, but the mechanisms underlying the aggressiveness of certain subtypes remain widely enigmatic. The aim of this study was to dissect the clinical and biological role of telomerase reactivation, a frequent mechanism of cancer cells to evade cellular senescence, in pediatric ependymoma.

Methods
We determined telomerase enzymatic activity, hTERT mRNA expression, promoter methylation, and the rs2853669 single nucleotide polymorphism located in the hTERT promoter in a well-characterized cohort of pediatric intracranial ependymomas.

Results
In posterior fossa ependymoma group A (PF-EPN-A) tumors, telomerase activity varied and was significantly associated with dismal overall survival, whereas telomerase reactivation was present in all supratentorial RelA fusion-positive (ST-EPN-RELA) ependymomas. In silico analysis of methylation patterns showed that only these two subgroups harbor hypermethylated hTERT promoters suggesting telomerase reactivation via epigenetic mechanisms. Furthermore, chromosome 1q gain, a well-known negative prognostic factor, was strongly associated with telomerase reactivation in PF-EPN-A. Additional in silico analyses of gene expression data confirmed this finding and further showed enrichment of the E-twenty-six factor, Myc, and E2F target genes in 1q gained ependymomas. Additionally, 1q gained tumors showed elevated expression of ETV3, an E-twenty-six factor gene located on chromosome 1q.

Conclusion
Taken together we describe a subgroup-specific impact of telomerase reactivation on disease progression in pediatric ependymoma and provide preliminary evidence for the involved molecular mechanisms.
主題
chromosome 1q
ependymoma
promoter methylation
RelA fusion
telomerase
掲載誌名
Neuro-Oncology
19
9
開始ページ
1183
終了ページ
1194
ISSN
1522-8517
ISSN(Online)
1523-5866
発行日
2017-5-24
DOI
出版者
Society for Neuro-Oncology
資料タイプ
学術雑誌論文
ファイル形式
PDF
著者版/出版社版
出版社版
業績ID
e34479
部局
医学部