Probabilistic Radiographic Atlas of Glioblastoma Phenotypes
Probabilistic Radiographic Atlas of Glioblastoma Phenotypes
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DOI：
10.3174/ajnr.a3253
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发表时间：
2013-03-01
影响因子：
3.5
通讯作者：
Cloughesy, T. F.
中科院分区：
文献类型：
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作者：
Ellingson, B. M.;Lai, A.;Cloughesy, T. F.
来自500多名胶质母细胞瘤患者的图像被用于建立与遗传和生物学异常以及基于年龄的预后相对应的位置图谱。大多数胶质母细胞瘤生长到邻近脑室下区的脑室周围区域。MGMT启动子甲基化的肿瘤更常见于年轻患者的左颞叶、IDH 1突变型肿瘤、前神经基因表达亚型的患者以及最常见于额叶的缺乏PTEN缺失的肿瘤。IDH 1基因突变的MGMT甲基化肿瘤多发生于左额叶。EGFR扩增和EGFR变体3表达肿瘤最常见于左颞叶。肿瘤在左颞叶与良好的反应放疗和增加survival.Background和目的：肿瘤的位置是一个重要的预后因素胶质母细胞瘤，这可能反映了肿瘤前体细胞的遗传特征。本研究的目的是构建和分析反映术前肿瘤位置和相应的人口统计学，-omic和干预表型的概率放射学图谱，以提供深入了解潜在的利基位置的胶质母细胞瘤细胞的origin.MATERIALS和方法：术前解剖MR图像在507例原发胶质母细胞瘤进行了分析。将图像配准到立体定向空间，对肿瘤进行分割，并通过年龄、切除范围、MGMT甲基化、IDH 1突变、基因表达亚类、PTEN缺失、PTEN缺陷、EGFR扩增、EGFR变体3表达、从放疗开始的无进展生存期和从初始诊断开始的总生存期对肿瘤发生的立体特异性频率进行统计学分析。大多数胶质母细胞瘤生长到脑室下区附近的脑室周围白色物质区域。MGMT启动子甲基化的肿瘤更频繁地发生在左颞叶、患有胶质母细胞瘤的年轻患者、IDH 1突变型肿瘤、具有前神经基因表达亚型的肿瘤以及最频繁发生在额叶中的缺乏PTEN缺失的肿瘤中。具有IDH 1突变的MGMT甲基化肿瘤倾向于发生在左额叶。EGFR扩增和EGFR变体3表达肿瘤最常发生在左颞叶。一个类似的区域在左颞叶与良好的反应，放化疗和增加survival.CONCLUSIONS：放射学图谱的特定表型提供洞察重叠之间的预后变量，并可能有助于确定利基位置的癌细胞的起源。
Images from over 500 patients with glioblastoma were used to build location atlases corresponding to genetic and biologic abnormalities as well as prognosis based on age. Most glioblastomas grew into the periventricular regions adjacent to the subventricular zone. MGMT promoter methylated tumors occurred more frequently in the left temporal lobe in young patients, in IDH1 mutant tumors, in those having the proneural gene expression subtype, and in tumors lacking loss of PTEN that occurred most frequently in the frontal lobe. MGMT methylated tumors with IDH1 mutation tended to occur in the left frontal lobe. EGFR amplified and EGFR variant 3-expressing tumors were found most frequently in the left temporal lobe. Tumors in the left temporal lobe were associated with favorable response to radiochemotherapy and increased survival.BACKGROUND AND PURPOSE: Tumor location is a significant prognostic factor in glioblastoma, which may reflect the genetic profile of tumor precursor cells. The purpose of the current study was to construct and analyze probabilistic radiographic atlases reflecting preoperative tumor locations and corresponding demographic, -omic, and interventional phenotypes to provide insight into potential niche locations of glioblastoma cells of origin.MATERIALS AND METHODS: Preoperative anatomic MR images in 507 patients with de novo glioblastoma were analyzed. Images were registered to stereotactic space, tumors were segmented, and the stereospecific frequency of tumor occurrence was analyzed statistically by age, extent of resection, MGMT methylation, IDH1 mutation, gene expression subclassification, PTEN loss, PTEN deficiency, EGFR amplification, EGFR variant 3 expression, progression-free survival from the start of radiochemotherapy, and overall survival from initial diagnosis.RESULTS: Most glioblastomas grow into the periventricular white matter regions adjacent to the subventricular zone. MGMT promoter methylated tumors occur more frequently in the left temporal lobe, in young patients with glioblastoma, in IDH1 mutant tumors, in tumors having the proneural gene expression subtype, and in tumors lacking loss of PTEN occurring most frequently in the frontal lobe. MGMT methylated tumors with the IDH1 mutation tended to occur in the left frontal lobe. EGFR amplified and EGFR variant 3-expressing tumors occurred most frequently in the left temporal lobe. A similar region in the left temporal lobe was associated with favorable response to radiochemotherapy and increased survival.CONCLUSIONS: Radiographic atlases for specific phenotypes provide insight into overlap between prognostic variables and may help to identify niche locations for cancer cells of origin.