成人 H3 K27M 突变型神经胶质瘤的特征。
Characteristics of H3 K27M-mutant gliomas in adults.
机构信息
Hospices Civils de Lyon, Groupe Hospitalier Est, Service de Neuropathologie, Lyon, Cedex, France; Université Claude Bernard Lyon 1, Lyon, France; Department of Cancer Cell Plasticity, Cancer Research Centre of Lyon, INSERM U1052, CNRS UMR5286, Lyon, France; Hospices Civils de Lyon, Groupe Hospitalier Est, Service de Neuro-Oncologie, Lyon, Cedex, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Anatomie et Cytologie Pathologiques, Lyon, Cedex, France; CHU Toulouse, Hôpital de Rangueil, Service d'Anatomie et Cytologie Pathologique, Toulouse, France; CHU Toulouse, Hôpital Pierre-Paul Riquet, Service de Neurologie, Toulouse, France; CHU Saint-Etienne, Hôpital Nord, Service d'Anatomie et Cytologie Pathologique, Saint-Etienne, France; CHU de Tours, Hôpital Bretonneau, Service d'anatomie et cytologie pathologiques, Tours, Cedex, France; CHU de Nice, Hôpital Pasteur, Service d'anatomie et cytologie pathologiques, Nice, France; CHU de Nice, Hôpital Pasteur, Service de neurologie, Nice, France; Hospices Civils de Lyon, Groupe Hospitalier Est, Service de Neurochirurgie D, Lyon, Cedex, France; Institut NeuroMyoGene, INSERM 1217/CNRS 5310, Université de Lyon, Lyon, France.
出版信息
Neuro Oncol. 2017 Aug 1;19(8):1127-1134. doi: 10.1093/neuonc/now274.
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.
背景
弥漫性 H3 K27M 突变型神经胶质瘤主要发生在儿童中，但也可发生于成年人。本研究旨在描述成人 H3 K27M 突变型神经胶质瘤的特征。
方法
我们分析了 21 例成人 H3 K27M 突变型神经胶质瘤的特征，并与 135 例无组蛋白 H3 且无异柠檬酸脱氢酶（IDH）突变（IDH/H3 野生型）的成人弥漫性神经胶质瘤进行了比较。
结果
H3 K27M 突变型神经胶质瘤的中位诊断年龄为 32 岁（范围：18-82 岁）。所有肿瘤均位于中线部位（脊髓 6 例，丘脑 5 例，脑干 5 例，小脑 3 例，下丘脑 1 例，松果体区 1 例），且 IDH 和 BRAF-V600E 野生型。H3 K27M 突变的鉴定显著影响了 3 例（14%）患者的诊断，这些患者的组织学表现最初提示弥漫性低级别胶质瘤，也影响了 7 例（33%）患者的诊断，这些患者的病理分析在弥漫性神经胶质瘤、神经节胶质瘤或毛细胞星形细胞瘤之间犹豫不决。与 IDH/H3 野生型神经胶质瘤相比，H3 K27M 突变型神经胶质瘤的诊断年龄更早（32 岁 vs 64 岁，P<0.001），均位于中线部位（21/21 例 vs 21/130 例，P<0.001），甲基化 MGMT 启动子频率较低（1/21 例 vs 52/129 例，P=0.002），且缺乏 EGFR 扩增（0/21 例 vs 26/128 例，P=0.02）。H3 K27M 突变型神经胶质瘤的中位生存期为 19.6 个月，IDH/H3 野生型神经胶质瘤为 17 个月（P=0.3）。
结论
在成年人中，与儿童一样，H3 K27M 突变定义了一组独特的 IDH 野生型神经胶质瘤亚组，其特征为恒定的中线位置、MGMT 启动子甲基化率低和预后不良。
Zotero 插件