Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location

被引：202

作者：

Karremann, Michael ^{[1
]}

Gielen, Gerrit H. ^{[2
]}

Hoffmann, Marion ^{[3
]}

Wiese, Maria ^{[3
]}

Colditz, Niclas ^{[3
]}

Warmuth-Metz, Monika ^{[4
]}

Bison, Brigitte ^{[4
]}

Claviez, Alexander ^{[5
]}

van Vuurden, Dannis G. ^{[6
]}

von Bueren, Andre O. ^{[3
,7
]}

Gessi, Marco ^{[2
]}

Kuehnle, Ingrid ^{[3
]}

Hans, Volkmar H. ^{[8
,9
]}

Benesch, Martin ^{[10
]}

Sturm, Dominik ^{[11
]}

Kortmann, Rolf-Dieter ^{[12
]}

Waha, Andreas ^{[2
]}

Pietsch, Torsten ^{[2
]}

Kramm, Christof M. ^{[3
]}

机构：

[1] Heidelberg Univ, Med Fac Mannheim, Univ Med Ctr Mannheim, Dept Pediat & Adolescent Med, Mannheim, Germany

[2] Univ Hosp Bonn, Dept Neuropathol, Bonn, Germany

[3] Univ Med Ctr Goettingen, Dept Child & Adolescent Hlth, Div Pediat Hematol & Oncol, Gottingen, Germany

[4] Univ Hosp Wuerzburg, Dept Neuroradiol, Wurzburg, Germany

[5] Schleswig Holstein Med Univ Kiel, Dept Pediat, Kiel, Germany

[6] Vrije Univ Amsterdam, Med Ctr, Div Oncol Hematol, Dept Pediat, Amsterdam, Netherlands

[7] Univ Hosp Geneva, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, Geneva, Switzerland

[8] Univ Med Greifswald, Dept Pathol, Greifswald, Germany

[9] Evangel Krankenhaus Bielefeld, Inst Neuropathol, Bielefeld, Germany

[10] Med Univ Graz, Dept Pediat & Adolescent Med, Div Pediat Hematol & Oncol, Graz, Austria

[11] German Canc Res Ctr Heidelberg, Div Pediat Neurooncol, Heidelberg, Germany

[12] Univ Leipzig, Dept Radiotherapy & Radiat Oncol, Med Ctr, Leipzig, Germany

来源：

NEURO-ONCOLOGY | 2018年 / 20卷 / 01期

关键词：

children; diffuse midline glioma; high-grade glioma; histone H3; K27M mutation; GROSS TOTAL RESECTION; MALIGNANT GLIOMAS; GENETIC ALTERATIONS; PEDIATRIC-PATIENTS; HISTONE H3.3; H3F3A; GLIOBLASTOMA; SUBGROUPS; DEFINE; FREQUENCY;

D O I：

10.1093/neuonc/nox149

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. 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. 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. 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.

引用

页码：123 / 131

页数：9

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