Louis D N
Department of Pathology (Neuropathology), Massachusetts General Hospital, Boston 02114.
J Neuropathol Exp Neurol. 1994 Jan;53(1):11-21. doi: 10.1097/00005072-199401000-00002.
p53 mutation is most likely an integral early step in the formation of a subset of human diffuse, fibrillary astrocytomas, but is not a frequent event in other studied brain tumors. In astrocytomas, p53 mutations are clustered in the conserved regions of the gene and are predominantly single base pair transitions, frequently at CpG dinucleotides. These mutations result in mutant or truncated p53 proteins that lack the transcriptional activating ability to induce G1 arrest, DNA repair, apoptosis or differentiation. On the other hand, some astrocytomas without p53 mutations may accumulate wild-type protein, perhaps as a physiological response to DNA damage or deregulated proliferation in the tumor cells. Finally, while data on the p53 gene and protein studies in human brain tumors are accumulating rapidly, the clinical significance of such data remains unclear.
p53突变很可能是人类弥漫性、纤维性星形细胞瘤亚群形成过程中不可或缺的早期步骤，但在其他已研究的脑肿瘤中并非常见事件。在星形细胞瘤中，p53突变集中在该基因的保守区域，且主要是单碱基对转换，常发生在CpG二核苷酸处。这些突变导致突变型或截短型p53蛋白，它们缺乏诱导G1期阻滞、DNA修复、细胞凋亡或分化的转录激活能力。另一方面，一些没有p53突变的星形细胞瘤可能会积累野生型蛋白，这或许是肿瘤细胞对DNA损伤或增殖失调的一种生理反应。最后，虽然关于人脑肿瘤中p53基因和蛋白研究的数据迅速积累，但此类数据的临床意义仍不明确。
