Cardona Andrés Felipe, Rojas Leonardo, Wills Beatriz, Behaine José, Jiménez Enrique, Hakim Fernando, Useche Nicolás, Bermúdez Sonia, Arrieta Oscar, Mejía Juan Armando, Ramón Juan Fernando, Carranza Hernán, Vargas Carlos, Otero Jorge, González Diego, Rodríguez July, Ortiz León Darío, Cifuentes Hernando, Balaña Carmen
Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia (A.F.C., H.C., C.V., J.O.); Foundation for Clinical and Applied Cancer Research- FICMAC, Bogotá, Colombia (A.F.C., B.W., H.C., C.V., J.O., J.R.); Institute of Neuroscience, Universidad El Bosque, Bogotá, Colombia (A.F.C., J.B., E.J., F.H., N.U., S.B., D.G.); Internal Medicicine Depatment, Universidad del Bosque-Fundación Santa Fe de Bogotá, Bogotá, Colombia (B.W.); Clinical Oncology Department, Centro Javeriano de Oncología, Hospital Universitario San Ignacio, Bogotá, Colombia (L.R.); Neurosurgery Department, Fundación Santa Fe de Bogotá, Bogotá, Colombia (F.H., J.A.M., J.F.R., E.J.); Radiology Department, Division of Neuro-radiology, Fundación Santa Fe de Bogotá, Bogotá, Colombia (N.U., S.B.); Experimental Oncology Laboratory, Instituto Nacional de Cancerología (INCan), México City, México (O.A.); Clinical Oncology Department, Division of Neuro-Oncology, Clínica de Las Américas, Medellín, Colombia (L.D.O.); Neurosurgery Department, Clínica del Country, Bogotá, Colombia (H.C.); Medical Oncology Department, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain (C.B.).
Neurooncol Pract. 2016 Sep;3(3):164-172. doi: 10.1093/nop/npv061. Epub 2016 Jan 28.
Low-grade gliomas (LGGs) are classified by the World Health Organization as astrocytoma (DA), oligodendroglioma (OD), and mixed oligoastrocytoma (OA). TP53 mutation and 1p19q codeletion are the most-commonly documented molecular abnormalities. Isocitrate dehydrogenase (IDH) 1/2 mutations are frequent in LGGs; however, IDH-negative gliomas can also occur. Recent research suggests that ATRX plays a significant role in gliomagenesis.
We investigated p53 and Olig2 protein expression, and promoter methylation, 1p19q codeletion, IDH, and ATRX status in 63 Colombian patients with LGG. The overall survival (OS) rate was estimated and compared according to genotype.
The most common histology was DA, followed by OD and OA. mutations were found in 57.1% and MGMT+ (positive status of MGMT promoter methylation methyl-guanyl-methyl-transferase gene) in 65.1% of patients, while overexpression of p53 and Olig2 was present in 30.2% and 44.4%, respectively, and 1p19q codeletion in 34.9% of the patients. Overexpression of ATRX was analyzed in 25 patients, 16% tested positive and were also mutations in isocitrate dehydrogenase and negative 1p19q-codelition. The median follow-up was 15.8 months (95% CI, 7.6-42.0) and OS was 39.2 months (95% CI, 1.3-114). OS was positively and significantly affected by MGMT+, 1p19q codeletion, surgical intervention extent, and number of lobes involved. Multivariate analysis confirmed that MGMT methylation status and 1p19q codeletion affected OS.
This is the first study evaluating the molecular profile of Hispanic LGG patients. Findings confirmed the prognostic relevance of MGMT methylation and 1p19q codeletion, but do not support mutation as a relevant marker. The latter may be explained by sample size and selection bias. ATRX alterations were limited to patients with DA and were mutations in isocitrate dehydrogenase and negative 1p19q-codelition.
世界卫生组织将低级别胶质瘤（LGGs）分为星形细胞瘤（DA）、少突胶质细胞瘤（OD）和混合性少突星形细胞瘤（OA）。TP53突变和1p19q共缺失是最常记录的分子异常。异柠檬酸脱氢酶（IDH）1/2突变在LGGs中很常见；然而，IDH阴性的胶质瘤也可能发生。最近的研究表明，ATRX在胶质瘤发生中起重要作用。
我们调查了63例哥伦比亚LGG患者的p53和Olig2蛋白表达、启动子甲基化、1p19q共缺失、IDH和ATRX状态。根据基因型估计并比较总生存率（OS）。
最常见的组织学类型是DA，其次是OD和OA。57.1%的患者发现 突变，65.1%的患者MGMT+（MGMT启动子甲基化甲基鸟嘌呤甲基转移酶基因阳性状态），而p53和Olig2的过表达分别出现在30.2%和44.4%的患者中，34.9%的患者存在1p19q共缺失。对25例患者分析了ATRX的过表达，16%检测为阳性，且也是异柠檬酸脱氢酶突变和1p19q共缺失阴性。中位随访时间为15.8个月（95%CI，7.6 - 42.0），OS为39.2个月（95%CI，1.3 - 114）。MGMT+、1p19q共缺失、手术干预范围和受累脑叶数量对OS有正向且显著的影响。多因素分析证实MGMT甲基化状态和1p19q共缺失影响OS。
这是第一项评估西班牙裔LGG患者分子特征的研究。研究结果证实了MGMT甲基化和1p19q共缺失的预后相关性，但不支持 突变作为一个相关标志物。后者可能由样本量和选择偏倚来解释。ATRX改变仅限于DA患者，且是异柠檬酸脱氢酶突变和1p19q共缺失阴性。
