Details

Autor(en) / Beteiligte

• Wu, Gang
• Diaz, Alexander K
• Paugh, Barbara S
• Rankin, Sherri L
• Ju, Bensheng
• Li, Yongjin
• Zhu, Xiaoyan
• Qu, Chunxu
• Chen, Xiang
• Zhang, Junyuan
• Easton, John
• Edmonson, Michael
• Ma, Xiaotu
• Lu, Charles
• Nagahawatte, Panduka
• Hedlund, Erin
• Rusch, Michael
• Pounds, Stanley
• Lin, Tong
• Onar-Thomas, Arzu
• Huether, Robert
• Kriwacki, Richard
• Parker, Matthew
• Gupta, Pankaj
• Becksfort, Jared
• Wei, Lei
• Mulder, Heather L
• Boggs, Kristy
• Vadodaria, Bhavin
• Yergeau, Donald
• Russell, Jake C
• Ochoa, Kerri
• Fulton, Robert S
• Fulton, Lucinda L
• Jones, Chris
• Boop, Frederick A
• Broniscer, Alberto
• Wetmore, Cynthia
• Gajjar, Amar
• Ding, Li
• Mardis, Elaine R
• Wilson, Richard K
• Taylor, Michael R
• Downing, James R
• Ellison, David W
• Zhang, Jinghui
• Baker, Suzanne J

Titel

The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma

Ist Teil von

• Nature genetics, 2014-05, Vol.46 (5), p.444-450

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem.