Davies M P, Gibbs F E, Halliwell N, Joyce K A, Roebuck M M, Rossi M L, Salisbury J, Sibson D R, Tacconi L, Walker C
JK Douglas Cancer Research Laboratory, Clatterbridge Hospital, Bebington, Merseyside, UK.
Br J Cancer. 1999 Mar;79(9-10):1542-8. doi: 10.1038/sj.bjc.6690246.
The PTEN gene, located on 10q23.3, has recently been described as a candidate tumour suppressor gene that may be important in the development of advanced cancers, including gliomas. We have investigated mutation in the PTEN gene by direct sequence analysis of PCR products amplified from samples microdissected from 19 low grade (WHO Grade I and II) and 27 high grade (WHO grade III and IV) archival, formalin-fixed, paraffin-embedded gliomas. Eleven genetic variants in ten tumours have been identified. Eight of these are DNA sequence changes that could affect the encoded protein and were present in 0/2 pilocytic astrocytomas, 0/2 oligoastrocytomas, 0/1 oligodendroglioma, 0/14 astrocytomas, 3/13 (23%) anaplastic astrocytomas and 5/14 (36%) glioblastomas. PTEN mutations were found exclusively in high grade gliomas; this finding was statistically significant. Only two of the PTEN genetic variants have been reported in other studies; two of the genetic changes are in codons in which mutations have not been found previously. The results of this study indicate that mutation in the PTEN gene is present only in histologically more aggressive gliomas, may be associated with the transition from low histological grade to anaplasia, but is absent from the majority of high grade gliomas.
位于10q23.3的PTEN基因最近被描述为一种候选肿瘤抑制基因，它在包括神经胶质瘤在内的晚期癌症发展中可能具有重要作用。我们通过对从19例低级别（世界卫生组织I级和II级）以及27例高级别（世界卫生组织III级和IV级）存档的、经福尔马林固定、石蜡包埋的神经胶质瘤中显微切割得到的样本所扩增的PCR产物进行直接序列分析，研究了PTEN基因的突变情况。在10个肿瘤中鉴定出了11种基因变异。其中8种是可能影响编码蛋白的DNA序列变化，它们在0/2例毛细胞型星形细胞瘤、0/2例少突星形细胞瘤、0/1例少突胶质细胞瘤、0/14例星形细胞瘤、3/13（23%）例间变性星形细胞瘤以及5/14（36%）例胶质母细胞瘤中出现。PTEN突变仅在高级别神经胶质瘤中被发现；这一发现具有统计学意义。在其他研究中仅报道了2种PTEN基因变异；其中2种基因变化位于此前未发现突变的密码子中。本研究结果表明，PTEN基因突变仅存在于组织学上侵袭性更强的神经胶质瘤中，可能与从低组织学级别向间变的转变相关，但在大多数高级别神经胶质瘤中不存在。
