Bigner S H, Matthews M R, Rasheed B K, Wiltshire R N, Friedman H S, Friedman A H, Stenzel T T, Dawes D M, McLendon R E, Bigner D D
Departments of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
Am J Pathol. 1999 Aug;155(2):375-86. doi: 10.1016/S0002-9440(10)65134-6.
Oligodendroglial neoplasms are a subgroup of gliomas with distinctive morphological characteristics. In the present study we have evaluated a series of these tumors to define their molecular profiles and to determine whether there is a relationship between molecular genetic parameters and histological pattern in this tumor type. Loss of heterozygosity (LOH) for 1p and 19q was seen in 17/23 (74%) well-differentiated oligodendrogliomas, in 18/23 (83%) anaplastic oligodendrogliomas, and in 3/8 (38%) oligoastrocytomas grades II and III. LOH for 17p and/or mutations of the TP53 gene occurred in 14 of these 55 tumors. Only one of the 14 cases with 17p LOH/TP53 gene mutation also had LOH for 1p and 19q, and significant astrocytic elements were seen histologically in the majority of these 14 tumors. LOH for 9p and/or deletion of the CDKN2A gene occurred in 15 of these 55 tumors, and 11 of these cases were among the 24 (42%) anaplastic oligodendrogliomas. Comparative genomic hybridization (CGH) identified the majority of cases with 1p and 19q loss and, in addition, showed frequent loss of chromosomes 4, 14, 15, and 18. These findings demonstrate that oligodendroglial neoplasms usually have loss of 1p and 19q whereas astrocytomas of the progressive type frequently contain mutations of the TP53 gene, and that 9p loss and CDKN2A deletions are associated with progression from well-differentiated to anaplastic oligodendrogliomas.
少突胶质细胞瘤是具有独特形态特征的胶质瘤亚群。在本研究中，我们评估了一系列此类肿瘤，以确定其分子谱，并确定该肿瘤类型中分子遗传参数与组织学模式之间是否存在关联。在23例分化良好的少突胶质细胞瘤中有17例（74%）出现1p和19q杂合性缺失（LOH），23例间变性少突胶质细胞瘤中有18例（83%）出现，8例II级和III级少突星形细胞瘤中有3例（38%）出现。在这55例肿瘤中，有14例出现17p LOH和/或TP53基因突变。在14例17p LOH/TP53基因突变的病例中，只有1例同时出现1p和19q LOH，并且在这14例肿瘤中的大多数在组织学上可见明显的星形细胞成分。在这55例肿瘤中，有15例出现9p LOH和/或CDKN2A基因缺失，其中11例在24例（42%）间变性少突胶质细胞瘤中。比较基因组杂交（CGH）确定了大多数1p和19q缺失的病例，此外，还显示出4号、14号、15号和18号染色体频繁缺失。这些发现表明，少突胶质细胞瘤通常有1p和19q缺失，而进展型星形细胞瘤经常含有TP53基因突变，并且9p缺失和CDKN2A基因缺失与从分化良好的少突胶质细胞瘤进展为间变性少突胶质细胞瘤有关。
