Details

Autor(en) / Beteiligte

• Prager, Briana C
• Vasudevan, Harish N
• Dixit, Deobrat
• Bernatchez, Jean A
• Wu, Qiulian
• Wallace, Lisa C
• Bhargava, Shruti
• Lee, Derrick
• King, Bradley H
• Morton, Andrew R
• Gimple, Ryan C
• Pekmezci, Melike
• Zhu, Zhe
• Siqueira-Neto, Jair L
• Wang, Xiuxing
• Xie, Qi
• Chen, Clark
• Barnett, Gene H
• Vogelbaum, Michael A
• Mack, Stephen C
• Chavez, Lukas
• Perry, Arie
• Raleigh, David R
• Rich, Jeremy N

Titel

The Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies

Ist Teil von

• Cancer discovery, 2020-11, Vol.10 (11), p.1722-1741

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Meningiomas are the most common primary intracranial tumor with current classification offering limited therapeutic guidance. Here, we interrogated meningioma enhancer landscapes from 33 tumors to stratify patients based upon prognosis and identify novel meningioma-specific dependencies. Enhancers robustly stratified meningiomas into three biologically distinct groups (adipogenesis/cholesterol, mesodermal, and neural crest) distinguished by distinct hormonal lineage transcriptional regulators. Meningioma landscapes clustered with intrinsic brain tumors and hormonally responsive systemic cancers with meningioma subgroups, reflecting progesterone or androgen hormonal signaling. Enhancer classification identified a subset of tumors with poor prognosis, irrespective of histologic grading. Superenhancer signatures predicted drug dependencies with superior efficacy to treatment based upon the genomic profile. Inhibition of DUSP1, a novel and druggable meningioma target, impaired tumor growth . Collectively, epigenetic landscapes empower meningioma classification and identification of novel therapies. SIGNIFICANCE: Enhancer landscapes inform prognostic classification of aggressive meningiomas, identifying tumors at high risk of recurrence, and reveal previously unknown therapeutic targets. Druggable dependencies discovered through epigenetic profiling potentially guide treatment of intractable meningiomas. .