TWiPO #25 ~ Histones in Pediatric Gliomas

April 05, 2012

Host Dr. Tim Cripe welcomes back co-host Dr. Lionel Chow to discuss somatic mutations in pediatric brain tumors. After recapping the consensus paper on molecular subgroups in medulloblastoma discussed in TWiPO episode 22 (Brain Tumor Round Robin) Dr Chow highlights the significance of the driver mutations in histone H3.3 in pediatric glioblastoma. Results of whole exome sequencing have shown that significantly more somatic mutations are present in adult tumors compared to pediatric tumors. This difference might suggest a reason for better success rates in pediatric tumors and possibly more escape mechanisms in adult tumors. Dr. Chow also discusses a paper published by the Pediatric Cancer Genome Project (a St. Jude Children's Research Hospital–Washington University collaboration) on somatic histone H3 alterations in diffuse intrinsic pontine glioma (DIPG). The findings are significant in showing that this mutation is present in 36% of non-brain stem gliomas and in 78% of brain stem gliomas, but in none of the other pediatric tumor types.

Please send comments and questions to twipo@solvingkidscancer.org

Papers discussed:

Taylor MD, Northcott PA, Korshunov A, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012 Apr;123(4):465-72. Epub 2011 Dec 2.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306779/

Schwartzentruber J, Korshunov A, Liu XY, Jones DT, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012 Jan 29;482(7384):226-31. doi: 10.1038/nature10833. http://www.ncbi.nlm.nih.gov/pubmed/22286061

Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, et al. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet. 2012 Jan 29;44(3):251-3. doi: 10.1038/ng.1102. St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project.http://www.ncbi.nlm.nih.gov/pubmed/22286216