Ersoy Tunc F, Keil Vera C, Hadizadeh Dariusch R, Gielen Gerrit H, Fimmers Rolf, Waha Andreas, Heidenreich Barbara, Kumar Rajiv, Schild Hans H, Simon Matthias
Department of Neurosurgery and Stereotaxy, University Hospital Bonn, Sigmund-Freud Straße 25, D-53105, Bonn, Germany.
Ev. Krankenhaus Bielefeld, Department of Neurosurgery, Kantensiek 11, D-33617, Bielefeld, Germany.
Neuroradiology. 2017 Dec;59(12):1223-1231. doi: 10.1007/s00234-017-1920-1. Epub 2017 Sep 11.
Magnetic resonance (MR) imaging biomarkers can assist in the non-invasive assessment of the genetic status in glioblastomas (GBMs). Telomerase reverse transcriptase (TERT) promoter mutations are associated with a negative prognosis. This study was performed to identify MR imaging biomarkers to forecast the TERT mutation status.
Pre-operative MRIs of 64/67 genetically confirmed primary GBM patients (51/67 TERT-mutated with rs2853669 polymorphism) were analyzed according to Visually AcceSAble Rembrandt Images (VASARI) ( https://wiki.cancerimagingarchive.net/display/Public/VASARI+Research+Project ) imaging criteria by three radiological raters. TERT mutation and O-methylguanine-DNA methyltransferase (MGMT) hypermethylation data were obtained through direct and pyrosequencing as described in a previous study. Clinical data were derived from a prospectively maintained electronic database. Associations of potential imaging biomarkers and genetic status were assessed by Fisher and Mann-Whitney U tests and stepwise linear regression.
No imaging biomarkers could be identified to predict TERT mutational status (alone or in conjunction with TERT promoter polymorphism rs2853669 AA-allele). TERT promoter mutations were more common in patients with tumor-associated seizures as first symptom (26/30 vs. 25/37, p = 0.07); these showed significantly smaller tumors [13.1 (9.0-19.0) vs. 24.0 (16.6-37.5) all cm; p = 0.007] and prolonged median overall survival [17.0 (11.5-28.0) vs. 9.0 (4.0-12.0) all months; p = 0.02]. TERT-mutated GBMs were underrepresented in the extended angularis region (p = 0.03), whereas MGMT-methylated GBMs were overrepresented in the corpus callosum (p = 0.03) and underrepresented temporomesially (p = 0.01).
Imaging biomarkers for prediction of TERT mutation status remain weak and cannot be derived from the VASARI protocol. Tumor-associated seizures are less common in TERT mutated glioblastomas.
磁共振（MR）成像生物标志物有助于对胶质母细胞瘤（GBM）的基因状态进行无创评估。端粒酶逆转录酶（TERT）启动子突变与不良预后相关。本研究旨在确定预测TERT突变状态的MR成像生物标志物。
根据可视可及的伦勃朗图像（VASARI）（https://wiki.cancerimagingarchive.net/display/Public/VASARI+Research+Project）成像标准，由三名放射科评估人员对64/67例经基因确诊的原发性GBM患者（51/67例TERT突变伴rs2853669多态性）的术前MRI进行分析。如先前研究所述，通过直接测序和焦磷酸测序获得TERT突变和O-甲基鸟嘌呤-DNA甲基转移酶（MGMT）高甲基化数据。临床数据来自前瞻性维护的电子数据库。通过Fisher检验、Mann-Whitney U检验和逐步线性回归评估潜在成像生物标志物与基因状态之间的关联。
未发现可预测TERT突变状态的成像生物标志物（单独或与TERT启动子多态性rs2853669 AA等位基因联合）。以肿瘤相关癫痫为首发症状的患者中TERT启动子突变更为常见（26/30 vs. 25/37，p = 0.07）；这些患者的肿瘤明显更小[均为厘米，13.1（9.0 - 19.0）vs. 24.0（16.6 - 37.5）；p = 0.007]，中位总生存期延长[均为月，17.0（11.5 - 28.0）vs. 9.0（4.0 - 12.0）；p = 0.02]。TERT突变的GBM在扩展角回区域的比例较低（p = 0.03），而MGMT甲基化的GBM在胼胝体中的比例较高（p = 0.03），在颞叶内侧的比例较低（p = 0.01）。
预测TERT突变状态的成像生物标志物仍然较弱，无法从VASARI方案中得出。肿瘤相关癫痫在TERT突变的胶质母细胞瘤中较少见。
