Abstract PR03: The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
Authors: Alexander K. Diaz, Gang Wu, Barbara S. Paugh, Yongjin Li, Xiaoyan Zhu, Sherri Rankin, Chunxu Qu, Xiang Chen, Junyuan Zhang, John Easton, Michael Edmonson, Charles Lu, Panduka Nagahawatte, Erin Hedlund, Michael Rusch, Stanley Pounds, Tong Lin, Arzu Onar-Thomas, Robert Huether, Richard Kriwacki, Matthew Parker, Pankaj Gupta, Jared Becksfort, Lei Wei, Heather L. Mulder, Kristy Boggs, Bhavin Vadodaria, Donald Yergeau, Kerri Ochoa, Robert S. Fulton, Lucinda S. Fulton, Chris Jones, Alberto Broniscer, Cynthia Wetmore, Amar Gajjar, Li Ding, Elaine R. Mardis, Richard K. Wilson, James R. Downing, David W. Ellison, Jinghui Zhang, Suzanne J. Baker
Journal: Cancer Research (2014)

Abstract Pediatric high-grade glioma (HGG) remains a tremendous clinical challenge, with a two-year survival of less than 20%. 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. Somatic mutations in the bone morphogenetic protein (BMP) receptor ACVR1 occurred in 32% of DIPG, a finding exclusive to brainstem HGG. Structural variants generating fusion genes were found in 47% of pediatric HGG, with recurrent fusions involving the neurotrophin receptor genes NTRK1, 2, or 3 in 40% of infant NBS-HGGs and 5% of pediatric HGG overall. Multiple mutations targeted pathways involving histone modification or chromatin remodeling, cell cycle regulation and receptor tyrosine kinase/RAS/PI3K signaling, in both DIPG and NBS-HGGs at frequencies of greater than 39% in the entire cohort. The HGG mutation burden ranged from 2 non-silent mutations in an infant HGG to more than a million mutations in a tumor associated with germline mismatch repair deficiency. From these findings, we have established novel tumor models to better understand this devastating disease. This work provides new insight into the genetic events driving pediatric HGG tumorigenesis. This abstract is also presented as Poster B14. Citation Format: Alexander K. Diaz, Gang Wu, Barbara S. Paugh, Yongjin Li, Xiaoyan Zhu, Sherri Rankin, Chunxu Qu, Xiang Chen, Junyuan Zhang, John Easton, Michael Edmonson, Charles Lu, Panduka Nagahawatte, Erin Hedlund, Michael Rusch, Stanley Pounds, Tong Lin, Arzu Onar-Thomas, Robert Huether, Richard Kriwacki, Matthew Parker, Pankaj Gupta, Jared Becksfort, Lei Wei, Heather L. Mulder, Kristy Boggs, Bhavin Vadodaria, Donald Yergeau, Kerri Ochoa, Robert S. Fulton, Lucinda S. Fulton, Chris Jones, Alberto Broniscer, Cynthia Wetmore, Amar Gajjar, Li Ding, Elaine R. Mardis, Richard K. Wilson, James R. Downing, David W. Ellison, Jinghui Zhang, Suzanne J. Baker, For the St Jude Children's Research Hospital – Washington University Pediatric Cancer Genome Project. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr PR03.