Format:
18
ISSN:
2159-8290
Content:
Molecular groups of supratentorial ependymomas comprise tumors with ZFTA-RELA or YAP1-involving fusions and fusion-negative subependymoma. However, occasionally supratentorial ependymomas cannot be readily assigned to any of these groups due to lack of detection of a typical fusion and/or ambiguous DNA methylation-based classification. An unbiased approach with a cohort of unprecedented size revealed distinct methylation clusters composed of tumors with ependymal but also various other histologic features containing alternative translocations that shared ZFTA as a partner gene. Somatic overexpression of ZFTA-associated fusion genes in the developing cerebral cortex is capable of inducing tumor formation in vivo, and cross-species comparative analyses identified GLI2 as a key downstream regulator of tumorigenesis in all tumors. Targeting GLI2 with arsenic trioxide caused extended survival of tumor-bearing animals, indicating a potential therapeutic vulnerability in ZFTA fusion-positive tumors. - Significance: ZFTA-RELA fusions are a hallmark feature of supratentorial ependymoma. We find that ZFTA acts as a partner for alternative transcriptional activators in oncogenic fusions of supratentorial tumors with various histologic characteristics. Establishing representative mouse models, we identify potential therapeutic targets shared by ZFTA fusion-positive tumors, such as GLI2.This article is highlighted in the In This Issue feature, p. 2113
Note:
Gesehen am 29.10.2021
In:
Cancer discovery, Philadelphia, Pa. : [Verlag nicht ermittelbar], 2011, 11(2021), 9, Seite 2230-2247, 2159-8290
In:
volume:11
In:
year:2021
In:
number:9
In:
pages:2230-2247
In:
extent:18
Language:
English
DOI:
10.1158/2159-8290.CD-20-0963
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