Steed Tyler C, Treiber Jeffrey M, Patel Kunal, Ramakrishnan Valya, Merk Alexander, Smith Amanda R, Carter Bob S, Dale Anders M, Chow Lionel M L, Chen Clark C
Center for Theoretical and Applied Neuro-Oncology, Division of Neurosurgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Weill-Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA.
Oncotarget. 2016 May 3;7(18):24899-907. doi: 10.18632/oncotarget.8551.
The subventricular zone (SVZ) has been implicated in the pathogenesis of glioblastoma. Whether molecular subtypes of glioblastoma arise from unique niches of the brain relative to the SVZ remains largely unknown. Here, we tested whether these subtypes of glioblastoma occupy distinct regions of the cerebrum and examined glioblastoma localization in relation to the SVZ.
Pre-operative MR images from 217 glioblastoma patients from The Cancer Imaging Archive were segmented automatically into contrast enhancing (CE) tumor volumes using Iterative Probabilistic Voxel Labeling (IPVL). Probabilistic maps of tumor location were generated for each subtype and distances were calculated from the centroid of CE tumor volumes to the SVZ. Glioblastomas that arose in a Genetically Modified Murine Model (GEMM) model were also analyzed with regard to SVZ distance and molecular subtype.
Classical and mesenchymal glioblastomas were more diffusely distributed and located farther from the SVZ. In contrast, proneural and neural glioblastomas were more likely to be located in closer proximity to the SVZ. Moreover, in a GFAP-CreER; PtenloxP/loxP; Trp53loxP/loxP; Rb1loxP/loxP; Rbl1-/- GEMM model of glioblastoma where tumor can spontaneously arise in different regions of the cerebrum, tumors that arose near the SVZ were more likely to be of proneural subtype (p < 0.0001).
Glioblastoma subtypes occupy different regions of the brain and vary in proximity to the SVZ. These findings harbor implications pertaining to the pathogenesis of glioblastoma subtypes.
室管膜下区（SVZ）与胶质母细胞瘤的发病机制有关。胶质母细胞瘤的分子亚型是否源于相对于SVZ的大脑独特微环境在很大程度上仍不清楚。在此，我们测试了这些胶质母细胞瘤亚型是否占据大脑的不同区域，并研究了胶质母细胞瘤相对于SVZ的定位。
使用迭代概率体素标记（IPVL）将来自癌症影像存档的217例胶质母细胞瘤患者的术前MR图像自动分割为对比增强（CE）肿瘤体积。为每种亚型生成肿瘤位置的概率图，并计算从CE肿瘤体积的质心到SVZ的距离。还分析了在基因工程小鼠模型（GEMM）中发生的胶质母细胞瘤的SVZ距离和分子亚型。
经典型和间充质型胶质母细胞瘤分布更弥散，且距离SVZ更远。相比之下，神经前体细胞型和神经型胶质母细胞瘤更有可能位于更靠近SVZ的位置。此外，在GFAP-CreER；PtenloxP/loxP；Trp53loxP/loxP；Rb1loxP/loxP；Rbl1-/-胶质母细胞瘤GEMM模型中，肿瘤可在大脑的不同区域自发发生，在SVZ附近发生的肿瘤更有可能是神经前体细胞型（p < 0.0001）。
胶质母细胞瘤亚型占据大脑的不同区域，与SVZ的距离各不相同。这些发现对胶质母细胞瘤亚型的发病机制具有启示意义。
