Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location
| Autor: | Christof M. Kramm, André O. von Bueren, Marion Hoffmann, Brigitte Bison, Maria Wiese, Rolf-Dieter Kortmann, Monika Warmuth-Metz, Torsten Pietsch, Dominik Sturm, Marco Gessi, Michael Karremann, Ingrid Kühnle, Andreas Waha, Niclas Colditz, Volkmar Hans, Martin Benesch, Gerrit H. Gielen, Dannis G. van Vuurden, Alexander Claviez |
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| Přispěvatelé: | Pediatric surgery, CCA - Cancer biology and immunology, Paediatric Oncology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Oncology
Male Cancer Research medicine.medical_specialty Adolescent Mutation/genetics Tumor resection Clinical Investigations Histones 03 medical and health sciences Histone H3 0302 clinical medicine High-grade glioma Internal medicine Glioma medicine Mutational status Humans Clinical significance Tumor location Child Children H3 K27M Mutation Histones/genetics ddc:618 Brain Neoplasms business.industry Clinical course Diffuse midline glioma Brain Neoplasms/diagnosis/genetics/pathology medicine.disease Prognosis 3. Good health K27M mutation 030220 oncology & carcinogenesis Mutation Glioma/diagnosis/genetics/pathology Female Neurology (clinical) Neoplasm Grading business 030217 neurology & neurosurgery |
| Zdroj: | Neuro-Oncology, Vol. 20, No 1 (2018) pp. 123-131 Neuro-Oncology, 20(1), 123-131. Oxford University Press Neuro-oncology, 20(1), 123-131. Oxford University Press Karremann, M, Gielen, G H, Hoffmann, M, Wiese, M, Colditz, N, Warmuth-Metz, M, Bison, B, Claviez, A, van Vuurden, D G, von Bueren, A O, Gessi, M, Kühnle, I, Hans, V H, Benesch, M, Sturm, D, Kortmann, R-D, Waha, A, Pietsch, T & Kramm, C M 2018, ' Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location ', Neuro-Oncology, vol. 20, no. 1, pp. 123-131 . https://doi.org/10.1093/neuonc/nox149 |
| ISSN: | 1522-8517 |
| DOI: | 10.1093/neuonc/nox149 |
| Popis: | Background The novel entity of "diffuse midline glioma, H3 K27M-mutant" has been defined in the 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). Tumors of this entity arise in CNS midline structures of predominantly pediatric patients and are associated with an overall dismal prognosis. They are defined by K27M mutations in H3F3A or HIST1H3B/C, encoding for histone 3 variants H3.3 and H3.1, respectively, which are considered hallmark events driving gliomagenesis. Methods Here, we characterized 85 centrally reviewed diffuse gliomas on midline locations enrolled in the nationwide pediatric German HIT-HGG registry regarding tumor site, histone 3 mutational status, WHO grade, age, sex, and extent of tumor resection. Results We found 56 H3.3 K27M-mutant tumors (66%), 6 H3.1 K27M-mutant tumors (7%), and 23 H3-wildtype tumors (27%). H3 K27M-mutant gliomas shared an aggressive clinical course independent of their anatomic location. Multivariate regression analysis confirmed the significant impact of the H3 K27M mutation as the only independent parameter predictive of overall survival (P = 0.009). In H3 K27M-mutant tumors, neither anatomic midline location nor histopathological grading nor extent of tumor resection had an influence on survival. Conclusion These results substantiate the clinical significance of considering diffuse midline glioma, H3 K27M-mutant, as a distinct entity corresponding to WHO grade IV, carrying a universally fatal prognosis. |
| Databáze: | OpenAIRE |
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