Characteristics of H3 K27M-mutant gliomas in adults

被引：219

作者：

Meyronet, David ^{[1
,2
,3
]}

Esteban-Mader, Maud ^{[4
]}

Bonnet, Charlotte ^{[4
]}

Joly, Marie-Odile ^{[2
,5
]}

Uro-Coste, Emmanuelle ^{[6
]}

Amiel-Benouaich, Alexandra ^{[7
]}

Forest, Fabien ^{[8
]}

Rousselot-Denis, Cecilia ^{[9
]}

Burel-Vandenbos, Fanny ^{[10
]}

Bourg, Veronique ^{[11
]}

Guyotat, Jacques ^{[12
]}

Fenouil, Tanguy ^{[1
]}

Jouvet, Anne ^{[1
,2
]}

Honnorat, Jerome ^{[2
,4
,13
]}

Ducray, Francois ^{[2
,3
,4
]}

机构：

[1] Hosp Civils Lyon, Grp Hosp Est, Serv Neuropathol, 59 Bvd Pinel, F-69394 Lyon, France

[2] Univ Claude Bernard Lyon 1, Lyon, France

[3] CNRS, Dept Canc Cell Plast, Canc Res Ctr Lyon, INSERM,U1052,UMR5286, Lyon, France

[4] Hosp Civils Lyon, Grp Hosp Est, Serv Neurooncol, Lyon, France

[5] Hosp Civils Lyon, Hop Edouard Herriot, Serv Anat & Cytol Pathol, Lyon, France

[6] CHU Toulouse, Hop Rangueil, Serv Anat & Cytol Pathol, Toulouse, France

[7] CHU Toulouse, Hop Pierre Paul Riquet, Serv Neurol, Toulouse, France

[8] CHU St Etienne, Hop Nord, Serv Anat & Cytol Pathol, St Etienne, France

[9] CHU Tours, Hop Bretonneau, Serv Anat & Cytol Pathol, Tours, France

[10] CHU Nice, Hop Pasteur, Serv Anat & Cytol Pathol, Nice, France

[11] CHU Nice, Hop Pasteur, Serv Neurol, Nice, France

[12] Hosp Civils Lyon, Grp Hosp Est, Serv Neurochirurg D, Lyon, France

[13] Univ Lyon, Inst NeuroMyoGene, INSERM 1217, CNRS 5310, Lyon, France

来源：

NEURO-ONCOLOGY | 2017年 / 19卷 / 08期

关键词：

glioma; histone; H3; K27M; IDH; INTRINSIC PONTINE GLIOMA; TERT PROMOTER MUTATIONS; H3F3A K27M MUTATIONS; HIGH-GRADE GLIOMAS; PEDIATRIC GLIOBLASTOMA; PILOCYTIC ASTROCYTOMA; GLIONEURONAL TUMORS; DRIVER MUTATIONS; GENE-EXPRESSION; HISTONE H3.3;

D O I：

10.1093/neuonc/now274

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background. Diffuse H3 K27M-mutant gliomas occur primarily in children but can also be encountered in adults. The aim of this study was to describe the characteristics of H3 K27M-mutant gliomas in adults. Methods. We analyzed the characteristics of 21 adult H3 K27M-mutant gliomas and compared them with those of 135 adult diffuse gliomas without histone H3 and without isocitrate dehydrogenase (IDH) mutation (IDH/H3 wild type). Results. The median age at diagnosis in H3 K27M-mutant gliomas was 32 years (range: 18-82 y). All tumors had a midline location (spinal cord n = 6, thalamus n = 5, brainstem n = 5, cerebellum n = 3, hypothalamus n = 1, and pineal region n = 1) and were IDH and BRAF-V600E wild type. The identification of an H3 K27M mutation significantly impacted the diagnosis in 3 patients (14%) for whom the histological aspect initially suggested a diffuse low-grade glioma and in 7 patients (33%) for whom pathological analysis hesitated between a diffuse glioma, ganglioglioma, or pilocytic astrocytoma. Compared with IDH/H3 wild-type gliomas, H3 K27M-mutant gliomas were diagnosed at an earlier age (32 vs 64 y, P < .001), always had a midline location (21/21 vs 21/130, P < .001), less frequently had a methylated MGMT promoter (1/21 vs 52/129, P = .002), and lacked EGFR amplification (0/21 vs 26/128, P = .02). The median survival was 19.6 months in H3 K27M-mutant gliomas and 17 months in IDH/H3 wild-type gliomas (P = .3). Conclusion. In adults, as in children, H3 K27M mutations define a distinct subgroup of IDH wild-type gliomas characterized by a constant midline location, low rate of MGMT promoter methylation, and poor prognosis.

引用

页码：1127 / 1134

页数：8

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