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Child's Nervous System
Erschienen in: Child's Nervous System 1/2018

24.10.2017 | Original Paper

Significance of H3K27M mutation with specific histomorphological features and associated molecular alterations in pediatric high-grade glial tumors

verfasst von: Süheyla Uyar Bozkurt, A. Dagcinar, B. Tanrikulu, N. Comunoglu, B. C. Meydan, M. Ozek, B. Oz

Erschienen in: Child's Nervous System | Ausgabe 1/2018

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Abstract

Purpose

Pediatric high-grade gliomas (pHGGs) constitute almost 15% of all childhood brain tumors. Recurrent mutations such as H3K27M mutation in H3F3A and HIST1H3B genes encoding histone H3 and its variants were identified in approximately 30% of pediatric glioblastomas. This study aimed to ascertain the morphological and molecular characteristics of pHGGs with H3K27M mutation.

Methods

In total, 61 cases of pHGGs (anaplastic astrocytoma, 12; glioblastomas, 49) from four university hospitals were studied. The histomorphological features were examined and immunohistochemistry was performed to evaluate the mutation status of H3K27M, ATRX, IDH1, BRAF V600E, and p53 genes.

Results

The study comprised 25 females and 36 males (age range, 1–18 years) with a clinical follow-up of up to 108 months. From the total, 31 patients were positive for H3K27M mutation located in the midline, mostly in the pons and thalamus. H3K27M mutation was commonly associated with ATRX loss (32.3%) and p53 (74.2%) immunoreactivity with a co-expression rate of 25.8%. While IDH1 mutation was not detected in pHGGs with H3K27M mutation, BRAFV600E mutation was rarely observed. Among the various histomorphological features, increased number of mitosis, increased Ki-67 proliferation index, and palisading and geographical necrosis along with small cell patterns were significantly associated with the H3K27M wild-type tumors. Focal infarct-like necrosis and pilomyxoid morphology was significantly associated with these tumors.

Conclusion

H3K27M mutation occurs exclusively in pHGGs arising from the midline and presents with varied histomorphological features ranging from low-grade pilomyxoid astrocytoma to highly pleomorphic glioblastoma along with ATRX loss and p53 mutations.
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Metadaten
Titel
Significance of H3K27M mutation with specific histomorphological features and associated molecular alterations in pediatric high-grade glial tumors
verfasst von
Süheyla Uyar Bozkurt
A. Dagcinar
B. Tanrikulu
N. Comunoglu
B. C. Meydan
M. Ozek
B. Oz
Publikationsdatum
24.10.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Child's Nervous System / Ausgabe 1/2018
Print ISSN: 0256-7040
Elektronische ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-017-3633-5

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