Department of Pathology, St. Olavs University Hospital, Trondheim, Norway.
Departments of Clinical and Molecular Medicine, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
J Neurooncol. 2020 Mar;147(1):147-157. doi: 10.1007/s11060-020-03409-8. Epub 2020 Jan 25.
According to the stem cell theory, two neurogenic niches in the adult human brain may harbor cells that initiate the formation of gliomas: The larger subventricular zone (SVZ) and the subgranular zone (SGZ) in the hippocampus. We wanted to explore whether defining molecular markers in low-grade gliomas (LGG; WHO grade II) are related to distance to the neurogenic niches.
Patients treated at two Norwegian university hospitals with population-based referral were included. Eligible patients had histopathological verified supratentorial low-grade glioma. IDH mutational status and 1p19q co-deletion status was retrospectively assessed. 159 patients were included, and semi-automatic tumor segmentation was done from pre-treatment T2-weighted (T2W) or Fluid-Attenuated Inversion Recovery (FLAIR) images. 3D maps showing the anatomical distribution of the tumors were then created for each of the three molecular subtypes (IDH mutated/1p19q co-deleted, IDH mutated and IDH wild-type). Both distance from tumor center and tumor border to the neurogenic niches were recorded.
In this population-based cohort of previously untreated low-grade gliomas, we found that low-grade gliomas are more often found closer to the SVZ than the SGZ, but IDH wild-type tumors are more often found near SGZ.
Our study suggests that the stem cell origin of IDH wild-type and IDH mutated low-grade gliomas may be different.
根据干细胞理论,成人脑中可能存在两个神经发生龛,这些龛可能含有启动神经胶质瘤形成的细胞:较大的侧脑室下区(SVZ)和海马的颗粒下区(SGZ)。我们想探讨低级别胶质瘤(LGG;WHO 分级 II)中定义的分子标志物是否与靠近神经发生龛的距离有关。
纳入在两家挪威大学医院接受以人群为基础转诊治疗的患者。合格的患者具有经组织病理学证实的幕上低级别胶质瘤。回顾性评估 IDH 突变状态和 1p19q 共缺失状态。纳入 159 例患者,从治疗前 T2 加权(T2W)或液体衰减反转恢复(FLAIR)图像中进行半自动肿瘤分割。然后为三种分子亚型(IDH 突变/1p19q 共缺失、IDH 突变和 IDH 野生型)中的每一种创建显示肿瘤解剖分布的 3D 图谱。记录肿瘤中心和肿瘤边界到神经发生龛的距离。
在这个基于人群的未经治疗的低级别胶质瘤队列中,我们发现低级别胶质瘤更常靠近 SVZ,而不是 SGZ,但 IDH 野生型肿瘤更常靠近 SGZ。
我们的研究表明,IDH 野生型和 IDH 突变型低级别胶质瘤的干细胞起源可能不同。