Details

Autor(en) / Beteiligte

• Zimmerman, Mark W
• Liu, Yu
• He, Shuning
• Durbin, Adam D
• Abraham, Brian J
• Easton, John
• Shao, Ying
• Xu, Beisi
• Zhu, Shizhen
• Zhang, Xiaoling
• Li, Zhaodong
• Weichert-Leahey, Nina
• Young, Richard A
• Zhang, Jinghui
• Look, A Thomas

Titel

MYC Drives a Subset of High-Risk Pediatric Neuroblastomas and Is Activated through Mechanisms Including Enhancer Hijacking and Focal Enhancer Amplification

Ist Teil von

• Cancer discovery, 2018-03, Vol.8 (3), p.320-335

Ort / Verlag

United States

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The amplified gene serves as an oncogenic driver in approximately 20% of high-risk pediatric neuroblastomas. Here, we show that the family member is a potent transforming gene in a separate subset of high-risk neuroblastoma cases (∼10%), based on (i) its upregulation by focal enhancer amplification or genomic rearrangements leading to enhancer hijacking, and (ii) its ability to transform neuroblastoma precursor cells in a transgenic animal model. The aberrant regulatory elements associated with oncogenic activation include focally amplified distal enhancers and translocation of highly active enhancers from other genes to within topologically associating domains containing the gene locus. The clinical outcome for patients with high levels of expression is virtually identical to that of patients with amplification of the gene, a known high-risk feature of this disease. Together, these findings establish as a bona fide oncogene in a clinically significant group of high-risk childhood neuroblastomas. Amplification of the oncogene is a recognized hallmark of high-risk pediatric neuroblastoma. Here, we demonstrate that is also activated as a potent oncogene in a distinct subset of neuroblastoma cases through either focal amplification of distal enhancers or enhancer hijacking mediated by chromosomal translocation. .