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Review
. 2017 Aug 1;19(8):1025-1034.
doi: 10.1093/neuonc/nox021.

Diffuse intrinsic pontine gliomas-current management and new biologic insights. Is there a glimmer of hope?

Kenneth J Cohen  1 , Nada Jabado  1 , Jacques Grill  1
Affiliations
Review

Diffuse intrinsic pontine gliomas-current management and new biologic insights. Is there a glimmer of hope?

Kenneth J Cohen et al. Neuro Oncol. .

Abstract

Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies have been undertaken-all of which have had a negligible impact on the natural history of this disease. More recently, improvements in neurosurgical techniques have allowed for the safe upfront biopsy of DIPG, which, together with a wider use of autopsy tissue, has led to an evolving understanding of the biology of this tumor. The discovery of a recurrent somatic gain-of-function mutation leading to lysine 27 to methionine (p.Lys27Met, K27M) substitution in histone 3 variants characterizes more than 85% of DIPG, suggesting for the first time the role of the epigenome and histones in the pathogenesis of this disease, and more unified diagnostic criteria. Along with further molecular insights into the pathogenesis of DIPG, rational targets are being identified and studied in the hopes of improving the otherwise dismal outcome for children with DIPG.

Keywords: DIPG; H3K27M; epigenetics; oncohistone.

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Figures

Fig. 1
Fig. 1
Classic imaging appearance of DIPG at diagnosis. MRI panels of these axial images demonstrate an enlarged pons with minimal contrast enhancement after the administration of gadolinium. Fluid attenuated inversion recovery imaging further elucidates the extent of involvement and demonstrates the envelopment of the basilar artery.
Fig. 2
Fig. 2
Known oncohistone mutations in human disease. Three specific residues in the histone 3 tail schematized at the amino acid level in the top panel are affected in cancer. Oncohistones are associated with cancers of ectomesenchyme origin in children and young adults, namely high-grade astrocytomas (HGA), chondroblastomas, giant cell tumors of the bone, and rarely acute T-cell lymphoblastic leukemias. K27M mutations target H3.3 and H3.1 variants and specify HGA of the brain midline. G34X exclusively targets noncanonical H3.3: H3F3A/G34R/V specifies HGA of the cortex while H3F3B/G34W specifies giant cell tumors of bone. H3.3 K36M mutations are identified in chondroblastoma. Note that oncohistones in HGA show specific associated mutations and brain location.
Fig. 3
Fig. 3
Identified subtypes of DIPG. Response to RT (Response to Radiotherapy); leptomeningeal metastases (at any time during the course of the disease).
See this image and copyright information in PMC

Comment in

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