Kraus J A, Koopmann J, Kaskel P, Maintz D, Brandner S, Schramm J, Louis D N, Wiestler O D, von Deimling A
Institut für Neuropathologie, Universitätskliniken Bonn, Germany.
J Neuropathol Exp Neurol. 1995 Jan;54(1):91-5. doi: 10.1097/00005072-199501000-00011.
Loss of heterozygosity (LOH) in specific chromosomal regions, which are likely to harbor tumor suppressor genes, has been associated with human gliomas. In this study we have analyzed astrocytic and oligodendroglial tumors for LOH on chromosomes 1 and 19. By microsatellite analysis LOH was found on chromosome arm 1p in 6/15 oligodendrogliomas WHO grade II and III, 12/25 oligoastrocytomas WHO grade II and III, 6/79 glioblastomas WHO grade IV, 5/44 astrocytomas WHO grade II and III and 0/23 pilocytic astrocytomas WHO grade I. The high incidence of LOH on chromosome arm 1p in oligodendrogliomas and oligoastrocytomas indicates that a putative tumor suppressor gene in this region is involved in the formation of gliomas with oligodendroglial features. Furthermore, the frequent involvement of chromosome arm 1p in oligodendrogliomas and oligoastrocytomas, but not in astrocytomas, suggests that genetically oligoastrocytoma is more similar to oligodendroglioma than to astrocytoma. In order to support this hypothesis, oligodendroglial and astrocytic areas in three mixed oligoastrocytomas were examined differentially for LOH 1p and for LOH 19q, the second genetic region believed to be affected in these tumors. All three tumors had LOH of 1p and LOH of 19q in both areas of oligodendroglial and of astrocytic differentiation. These findings show that the astrocytic and oligodendroglial portions of oligoastrocytoma share molecular genetic features and probably are of monoclonal origin.
特定染色体区域杂合性缺失（LOH）可能与肿瘤抑制基因相关，这一现象已在人类胶质瘤中有所发现。在本研究中，我们分析了星形细胞瘤和少突胶质细胞瘤中1号和19号染色体上的LOH情况。通过微卫星分析发现，在WHO二级和三级少突胶质细胞瘤的15例中有6例出现1p染色体臂LOH，WHO二级和三级少突星形细胞瘤的25例中有12例出现，WHO四级胶质母细胞瘤的79例中有6例出现，WHO二级和三级星形细胞瘤的44例中有5例出现，而WHO一级毛细胞型星形细胞瘤的23例中未出现。少突胶质细胞瘤和少突星形细胞瘤中1p染色体臂LOH的高发生率表明，该区域的一个假定肿瘤抑制基因参与了具有少突胶质细胞特征的胶质瘤的形成。此外，1p染色体臂在少突胶质细胞瘤和少突星形细胞瘤中频繁受累，而在星形细胞瘤中未受累，这表明在遗传学上少突星形细胞瘤与少突胶质细胞瘤比与星形细胞瘤更为相似。为了支持这一假设，我们对3例混合性少突星形细胞瘤中的少突胶质细胞和星形细胞区域分别检测了1p LOH和19q LOH，后者是另一个被认为在这些肿瘤中受影响的基因区域。所有3例肿瘤在少突胶质细胞分化区域和星形细胞分化区域均出现了1p LOH和19q LOH。这些发现表明，少突星形细胞瘤的星形细胞和少突胶质细胞部分具有共同的分子遗传学特征，可能起源于单克隆。
