Bello M J, de Campos J M, Kusak M E, Vaquero J, Sarasa J L, Pestaña A, Rey J A
Instituto de Investigaciones Biomédicas (CSIC), Madrid, Spain.
Cancer Genet Cytogenet. 1994 Apr;73(2):122-9. doi: 10.1016/0165-4608(94)90195-3.
A series of 57 malignant gliomas, including 27 astrocytomas grade III-IV (glioblastoma multiforme), 15 astrocytomas grade I-II, and 15 tumors with major oligodendroglial component, was examined to detect molecular abnormalities of loci at specific chromosome regions. At the cytogenetic level, these regions have been shown to be nonrandomly involved in neoplastic development of these histologic subtypes of tumor. We used a panel of 24 polymorphic DNA probes to analyze loss of heterozygosity (LOH) at loci on chromosomes 7, 9, 10, 13, 17p, and 22q. In addition, the retinoblastoma (RB1) oncosuppressor gene, the platelet-derived growth factor A (PDGFA) gene, and the epidermal growth factor receptor (EGFR) gene were analyzed directly. Loss of genetic information on the short arm of chromosome 17 was observed in both low- and high-grade astrocytomas, whereas no oligodendroglial tumor was characterized by this type of aberration. LOH for chromosome 10, mainly compatible with loss of the entire chromosome, was primarily evidenced in the more malignant forms and in isolated cases diagnosed as low-grade astrocytomas. Again, no oligodendroglial tumor displayed losses of chromosome 10. In contrast, four tumors with major oligodendroglial component showed losses involving 9p markers, primarily interferon A and B (IFNA, IFNB); this feature was also observed in two low-grade astrocytomas and in 11 high-grade tumors. Isolated cases displayed LOH for markers on chromosomes 13 and 22, whereas EGFR amplification was almost exclusively evidenced in the more malignant forms which, in most instances, also presented LOH for chromosome 10. In general, the samples with lower malignancy stage displayed a lesser grade of abnormalities, mainly restricted to losses at 17p and chromosome 10 in astrocytomas grade I-II and at 9p in oligodendrogliomas. In contrast, about 50% of the high-grade tumor samples analyzed included abnormalities at two or more loci, with a recurrent association of EGFR amplification and LOH for chromosome 10; this association was evident in 26% of the high-grade astrocytomas.
对57例恶性胶质瘤进行了研究，其中包括27例III - IV级星形细胞瘤（多形性胶质母细胞瘤）、15例I - II级星形细胞瘤以及15例主要由少突胶质细胞组成的肿瘤，以检测特定染色体区域位点的分子异常。在细胞遗传学水平上，这些区域已被证明在这些组织学亚型肿瘤的肿瘤发生过程中存在非随机参与情况。我们使用一组24个多态性DNA探针来分析7号、9号、10号、13号、17p号和22q号染色体上位点的杂合性缺失（LOH）。此外，还直接分析了视网膜母细胞瘤（RB1）抑癌基因、血小板衍生生长因子A（PDGFA）基因和表皮生长因子受体（EGFR）基因。在低级别和高级别星形细胞瘤中均观察到17号染色体短臂上的遗传信息缺失，而少突胶质细胞瘤未表现出这种类型的畸变。10号染色体的杂合性缺失主要与整条染色体的缺失相符，主要在更恶性的肿瘤形式以及个别诊断为低级别星形细胞瘤的病例中出现。同样，少突胶质细胞瘤未显示10号染色体缺失。相比之下，4例主要由少突胶质细胞组成的肿瘤显示涉及9p标记的缺失，主要是干扰素A和B（IFNA、IFNB）；在2例低级别星形细胞瘤和11例高级别肿瘤中也观察到了这一特征。个别病例显示13号和22号染色体上标记的杂合性缺失，而EGFR扩增几乎仅在更恶性的肿瘤形式中出现，在大多数情况下，这些肿瘤也表现出10号染色体杂合性缺失。总体而言，恶性程度较低阶段的样本异常程度较低，主要局限于I - II级星形细胞瘤中的17p和10号染色体缺失以及少突胶质细胞瘤中的9p缺失。相比之下，约50%的高级别肿瘤样本分析包括两个或更多位点的异常，EGFR扩增与10号染色体杂合性缺失反复关联；这种关联在26%的高级别星形细胞瘤中很明显。
