Bello M J, Leone P E, Vaquero J, de Campos J M, Kusak M E, Sarasa J L, Pestaña A, Rey J A
Instituto de Investigaciones Biomédicas (CSIC), Department of Neurosurgery, Madrid, Spain.
Int J Cancer. 1995 Jun 22;64(3):207-10. doi: 10.1002/ijc.2910640311.
The molecular mechanisms underlying the genesis and progression of oligodendroglial tumors are poorly understood, since only restricted information on loss of heterozygosity from isolated cases is available. The commonest alterations appear to involve deletion of 1p and 19q, while loss of heterozygosity for 9p, chromosome 10 or epidermal growth factor receptor gene amplification have been described in single tumors. We have applied restriction fragment length polymorphism analysis to 14 loci covering chromosome 1 and 7 loci on chromosome 19 in a series of 25 tumors with an oligodendroglial component to determine precisely the participation of these suppressor genes in the genesis of tumors. Twenty-two and 19 of the 25 samples displayed LOH at 1p and 19q, respectively, and both anomalies were detected in association in 17 samples, including low- and high-grade oligodendrogliomas as well as mixed oligo-astrocytomas. Our findings suggest that inactivation of tumor suppressor genes located on 1p and 19q represent cooperative alterations occurring at early stages of oncogenic transformation of oligodendroglial neoplasms.
少突胶质细胞瘤发生和进展的分子机制目前仍知之甚少，因为仅能从个别病例中获取关于杂合性缺失的有限信息。最常见的改变似乎涉及1p和19q的缺失，而9p、10号染色体的杂合性缺失或表皮生长因子受体基因扩增仅在个别肿瘤中被描述过。我们应用限制性片段长度多态性分析对一系列25例含有少突胶质细胞成分的肿瘤中覆盖1号染色体的14个位点和19号染色体的7个位点进行分析，以准确确定这些抑癌基因在肿瘤发生中的作用。25个样本中分别有22个和19个在1p和19q显示杂合性缺失，且在17个样本中同时检测到这两种异常，包括低级别和高级别少突胶质细胞瘤以及混合性少突星形细胞瘤。我们的研究结果表明，位于1p和19q上的肿瘤抑制基因失活代表了少突胶质细胞瘤致癌转化早期发生的协同改变。
