Patt S, Gries H, Giraldo M, Cervos-Navarro J, Martin H, Jänisch W, Brockmöller J
Institute of Neuropathology, Free University of Berlin, Germany.
Hum Pathol. 1996 Jun;27(6):586-9. doi: 10.1016/s0046-8177(96)90166-5.
Recent molecular biological studies have shown evidence for a distinct pathogenesis of pilocytic astrocytomas based on alterations other than mutations of the tumor suppressor gene p53. To prove these data, the authors screened a series of 42 astrocytic human brain tumors with a relatively high proportion (16.6%) of the pilocytic variant for the presence of p53 mutations, using the polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis, followed by DNA sequencing. Mutations were found in one of seven (14.3%) pilocytic astrocytomas, in one of 18 (5.6%) low grade astrocytomas, and in one of four (25%) anaplastic astrocytomas, but in none of 13 glioblastomas. Sites of missense mutations were in exon 8 (codons 281 and 282), and exon 5 (codon 151). Silent mutation was found in exon 9 (codon 324), which was related to pilocytic astrocytoma. This is, to the authors' knowledge, the first report that shows a p53 mutation in pilocytic astrocytomas. However, the p53 mutation was only found in one of seven tumors of this entity and was a silent mutation, which does not lead to change of amino acids. Thus, the significance of this alteration for the development of this special tumor type seems to be low. Nevertheless, it may be a sign of genetic instability and is thus suggested to be of certain pathogenetic relevance. The p53 findings concerning the other tumors are in accordance with the view of p53 gene mutations to be early events in astrocytoma formation.
近期分子生物学研究表明，基于肿瘤抑制基因p53突变以外的改变，毛细胞型星形细胞瘤具有独特的发病机制。为证实这些数据，作者采用聚合酶链反应（PCR）和单链构象多态性（SSCP）分析，随后进行DNA测序，对一系列42例人类星形细胞瘤进行筛查，其中毛细胞型变体比例相对较高（16.6%），以检测p53突变的存在。在7例毛细胞型星形细胞瘤中有1例（14.3%）、18例低级别星形细胞瘤中有1例（5.6%）、4例间变性星形细胞瘤中有1例（25%）发现了突变，但在13例胶质母细胞瘤中均未发现突变。错义突变位点在外显子8（密码子281和282）和外显子5（密码子151）。在外显子9（密码子324）发现了沉默突变，其与毛细胞型星形细胞瘤有关。据作者所知，这是首次报道毛细胞型星形细胞瘤中存在p53突变。然而，p53突变仅在该实体的7例肿瘤中的1例中发现，且为沉默突变，不会导致氨基酸改变。因此，这种改变对这种特殊肿瘤类型发展的意义似乎较低。尽管如此，它可能是基因不稳定的一个标志，因此被认为具有一定的致病相关性。关于其他肿瘤的p53研究结果与p53基因突变是星形细胞瘤形成早期事件的观点一致。
