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diffuse_intrinsic_pontine_glioma

Diffuse intrinsic pontine glioma

see also Diffuse midline glioma H3 K27M-mutant.

Diffuse midline glioma H3 K27M-mutant includes tumors previously referred to as diffuse intrinsic pontine glioma (DIPG). The identification of this phenotypically and molecularly defined set of tumors provides a rationale for therapies directed against the effects of these mutations.

Epidemiology

Approximately 300 children are diagnosed with diffuse intrinsic pontine gliomas (DIPG) each year, usually between the ages of 5 and 9.

They account for 10% to 25% of pediatric brain tumors.

The majority of DIPGs are astrocytic, infiltrative, and localized to the pons.

Etiology

The majority of the tumors were positive for GFAP (24/24), MIB1 (23/24), OLIG2 (22/24), p16 (20/24), p53 (20/24), SOX2 (19/24), EGFR (16/24), and BMI1 (9/24). The results suggest that dysregulation of EGFR and p53 may play an important role in the development of DIPGs. The majority of DIPGs express stem cell markers such as SOX2 and OLIG2, consistent with a role for tumor stem cells in the origin and maintenance of these tumors 1).

Results suggest that dual targeting of NOTCH and MYCN in DIPG may be an effective therapeutic strategy in DIPG and that adding a γ-secretase inhibitor during radiation therapy may be efficacious initially or during reirradiation 2).

Clinical Features

The symptoms of DIPG usually develop very rapidly prior to diagnosis, reflecting the fast growth of these tumors. Most patients start experiencing symptoms less than three months—and often less than three weeks—before diagnosis. The most common symptoms include:

Rapidly developing problems controlling eye movements, facial expressions, speech, chewing, and swallowing (due to problems in the cranial nerves) Weakness in the arms and legs

Problems with walking and coordination.

Treatment

Outcome

Complications

1)
Ballester LY, Wang Z, Shandilya S, Miettinen M, Burger PC, Eberhart CG, Rodriguez FJ, Raabe E, Nazarian J, Warren K, Quezado MM. Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas. Am J Surg Pathol. 2013 Sep;37(9):1357-64. doi: 10.1097/PAS.0b013e318294e817. PubMed PMID: 24076776; PubMed Central PMCID: PMC3787318.
2)
Taylor IC, Hütt-Cabezas M, Brandt WD, Kambhampati M, Nazarian J, Chang HT, Warren KE, Eberhart CG, Raabe EH. Disrupting NOTCH Slows Diffuse Intrinsic Pontine Glioma Growth, Enhances Radiation Sensitivity, and Shows Combinatorial Efficacy With Bromodomain Inhibition. J Neuropathol Exp Neurol. 2015 Jun 25. [Epub ahead of print] PubMed PMID: 26115193.
diffuse_intrinsic_pontine_glioma.txt · Last modified: 2019/03/18 23:48 by administrador