Meyer-Puttlitz B, Hayashi Y, Waha A, Rollbrocker B, Boström J, Wiestler O D, Louis D N, Reifenberger G, von Deimling A
Department of Neuropathology, University of Bonn Medical Center, Germany.
Am J Pathol. 1997 Sep;151(3):853-7.
Glioblastomas (GBMs) are a heterogeneous group of tumors. Recently, distinct molecular genetic alterations have been linked to subgroups of patients with GBM. Giant cell (gc)GBMs are a rare variant of GBM characterized by a marked preponderance of multinucleated giant cells. Several reports have associated this entity with a more favorable prognosis than the majority of GBMs. To evaluate whether gcGBM may also represent a genetically defined subgroup of GBM, we analyzed a series of 19 gcGBMs for mutations in the TP53 gene for amplification of the EGFR and CDK4 genes and for homozygous deletions in the CDKN2A (p16/MTS1) gene. Seventeen of nineteen gcGBMs carried TP53 mutations whereas EGFR and CDK4 gene amplification was seen in only one tumor each and homozygous deletion of CDKN2A was not observed at all. The strikingly high incidence of TP53 mutations and the relative absence of other genetic alterations groups gcGBM together with a previously recognized molecular genetic variant of GBM (type 1 GBM). It is tempting to speculate that the better prognosis of gcGBM patients may result from the low incidence of EGFR amplification and CDKN2A deletion, changes known for their growth-promoting potential.
胶质母细胞瘤（GBM）是一组异质性肿瘤。最近，不同的分子遗传学改变已与GBM患者的亚组相关联。巨细胞（gc）GBM是GBM的一种罕见变体，其特征是多核巨细胞明显占优势。几份报告表明，与大多数GBM相比，该实体的预后更有利。为了评估gcGBM是否也可能代表GBM的一个基因定义亚组，我们分析了19例gcGBM，检测其TP53基因突变、EGFR和CDK4基因扩增以及CDKN2A（p16/MTS1）基因的纯合缺失情况。19例gcGBM中有17例携带TP53突变，而EGFR和CDK4基因扩增仅在各1例肿瘤中出现，完全未观察到CDKN2A的纯合缺失。TP53突变的高发生率以及其他遗传改变的相对缺乏，将gcGBM与先前确认的GBM分子遗传学变体（1型GBM）归为一类。很容易推测，gcGBM患者较好的预后可能是由于EGFR扩增和CDKN2A缺失的发生率较低，而这些改变具有促进生长的潜力。
