Ⅱ/Ⅲ级成人弥漫性胶质瘤分子分型研究进展

Advances in molecular classification of diffuse WHO grade Ⅱ/Ⅲ glioma in adults

神经胶质瘤是最常见的原发性中枢神经系统恶性肿瘤,传统的组织学分级是预测肿瘤生物学行为的一种手段,也是确定治疗方案的重要依据。WHOⅡ/Ⅲ级弥漫性胶质瘤患者的生存期跨度较大,部分患者在数月内可进展为胶质母细胞瘤(Ⅳ级),部分患者则可多年维持病情稳定;部分患者对放化疗敏感,部分患者则不敏感。近年来的研究发现,分子分型较传统的仅基于病理学的分级能够更加准确地判断神经胶质瘤患者的预后。Ⅱ/Ⅲ级成人弥漫性胶质瘤可依据基因的变化分成不同预后的亚型。研究证实,几乎所有的Ⅱ/Ⅲ级弥漫性胶质瘤可首先依据异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)1/2基因的突变状态进行分型,其次是基于1p19q联合缺失状态以及X连锁α地中海贫血/精神发育迟滞综合征蛋白(alpha thalassemia/mental retardation syndrome X-linked,ATRX)基因和(或)肿瘤抑制蛋白p53(tumor supressor p53,TP53)基因突变状态作进一步的分型。IDH基因突变伴随1p19q联合缺失大多发生于少突胶质细胞瘤,并常伴随端粒酶逆转录酶(telomerase reverse transcriptase,TERT)基因启动子、远端上游结合蛋白1(far upstream element binding protein 1,FUBP1)基因、CIC基因和Notch1基因突变;而IDH野生型可以基于DNA甲基化状态而进一步分成预后不同的3种亚型。

Objective： Glioma is the most common malignant primary central nervous system tumor. The traditional histologic classification has been applied for predicting biological behavior of glioma and deciding the treatment strategy. The scope of survival in WHO grade Ⅱ/Ⅲ is very broad, some progress to glioblastoma in a few months, and some in stable for many years; some is sensitive to radiation and chemotherapy, but some are not sensitive. In recent years, the studies have found that the molecular classification is more accurate in judging prognosis than traditional histologic classification. Almost all grade Ⅱ/Ⅲ glioma can be separated into two subtypes according to mutation status of isocitrate dehydrogenase 1/2 （IDH1/2）, and further classification is based on 1 p19q, ATRX （alpha thalassemia/mental retardation syndrome X-linked） and TP53 （tumor protein p53） status. IDH mutation combined with 1p19q co-deletion most harbored in oligodendroglioma, often accompanies with mutation in CIC, far upstream element binding protein 1 （FUBP1）, Notch1 and telomerase reverse transcriptase （TERT） promoter. The IDH wild type can be further divided into three subtypes with different prognosis based on DNA-methylation platform.