组蛋白H3.3 G34R/V突变在神经胶质瘤中的研究进展

摘要

There are two genes encoding H3F3A and H3F3B in human histone H3.3 variant. The mutation rate of G34R/V is lower than that of K27M in high-grade glioma. H3.3 G34 mutation presents a histopathologically heterogeneous, with microscopic characteristics of typical glioblastoma (GBM), central nervous system primitive neuroectodermal tumors (CNS-PNET), or even astroblastoma. More-over, G34-mutant tumor has its unique manifestation in the age of onset, tumor location, and prognosis. CNS tumors with H3.3 G34 mutations displayed uniform epigenetic signatures, suggesting a single biological origin. Chromosome 3q and 4q deletions were more common and specific in G34-mutant tumors, which were often accompanied by PDGFRA or CCND2 amplification, than in other sub-types of GBM. Here, we review the clinicopathological and molecular genetic characteristics of histone H3.3 G34R/V mutant gliomas.%人组蛋白H3.3变体包含H3F3A和H3F3B两个编码基因,其中H3F3A突变的高级别胶质瘤中G34R/V突变率低于K27M,与后者在形态学上相对一致相比,H3.3 G34突变的肿瘤组织学具有明显异质性,镜下表现可以是经典的胶质母细胞瘤(glioblasto-ma,GBM),也可以是中枢神经系统原始神经外胚层肿瘤(central nervous system primitive neuroectodermal tumours,CNS-PNET),甚至星形母细胞瘤.H3.3 G34突变肿瘤在发病年龄、病变累及范围以及预后治疗上有其独特的表现.基因组和表观基因组学研究显示H3.3 G34突变的CNS肿瘤表现为一致的表观遗传学特征,提示其具有同一生物学起源.与其他GBM亚型细胞遗传学相比分析,G34突变的肿瘤3q和4q缺失的频率和特异性均较高,并常伴有PDGFRA或CCND2扩增.本文对组蛋白H3.3 G34R/V突变神经胶质瘤的临床病理特征及分子遗传学特点进行综述.