diffuse intrinsic pontine glioma
Thursday 15 July 2010
Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating of pediatric malignancies and one for which no effective therapy exists.
A major contributor to the failure of therapeutic trials is the assumption that biologic properties of brainstem tumors in children are identical to cerebral high-grade gliomas of adults.
Analysis of DIPG copy number alterations showed recurrent changes distinct from those of pediatric supratentorial high-grade astrocytomas.
Thirty-six percent of DIPGs had gains in platelet-derived growth factor receptor alpha (PDGFRA; 4 to 18 copies) and all showed PDGFR-alpha expression. (#20142589#)
Low-level gains in poly (ADP-ribose) polymerase-1 (PARP1) were identified in some cases. Pathway analysis revealed genes with loss of heterozygosity were enriched for DNA repair pathways. (#20142589#)
There are involvement of the PDGFR pathway as well as defects in DNA repair pathways coupled with gain of PARP-1 highlight two potential, biologically based, therapeutic targets directed specifically at this devastating disease. (#20142589#)
1q : 34%
Xq : 25%
2p : 22%
7p : 22%
14q : 31%
10q : 28%
17p : 25%
PTEN, CDKN2A, AKT1, CEBPB
Genomic aberrations in pediatric diffuse intrinsic pontine gliomas. Warren KE, Killian K, Suuriniemi M, Wang Y, Quezado M, Meltzer PS. Neuro Oncol. 2011 Nov 7. PMID: #22064882#
Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J, Bax DA, Coyle B, Barrow J, Hargrave D, Lowe J, Gajjar A, Zhao W, Broniscer A, Ellison DW, Grundy RG, Baker SJ. J Clin Oncol. 2010 Jun 20;28(18):3061-8. PMID: #20479398#
Homozygous loss of ADAM3A revealed by genome-wide analysis of pediatric high-grade glioma and diffuse intrinsic pontine gliomas. Barrow J, Adamowicz-Brice M, Cartmill M, MacArthur D, Lowe J, Robson K, Brundler MA, Walker DA, Coyle B, Grundy R. Neuro Oncol. 2011 Feb;13(2):212-22. PMID: #21138945#
Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. Zarghooni M, Bartels U, Lee E, Buczkowicz P, Morrison A, Huang A, Bouffet E, Hawkins C. J Clin Oncol. 2010 Mar 10;28(8):1337-44. PMID: #20142589#
Brainstem gliomas—a clinicopathological study of 45 cases with p53 immunohistochemistry. Badhe PB, Chauhan PP, Mehta NK. Indian J Cancer. 2004 Oct-Dec;41(4):170-4. PMID: #15659871# [Free]