Jen J, Harper J W, Bigner S H, Bigner D D, Papadopoulos N, Markowitz S, Willson J K, Kinzler K W, Vogelstein B
Johns Hopkins Oncology Center, Baltimore, Maryland 21231.
Cancer Res. 1994 Dec 15;54(24):6353-8.
We have used molecular genetic methods to examine the status of cell cycle-inhibitory genes in human brain tumors. We found that p16 and a neighboring gene, p15, were often homozygously deleted in glioblastoma multiformes but not in medulloblastomas or ependymomas. The deletions occurred in both primary tumors and their derived xenografts, but no intragenic mutations in either of the two genes were found. The p15 gene was expressed in a more widespread pattern in normal tissues than p16, but the products of both genes had similar capacities to bind to cyclin D-dependent kinases 4 and 6. These data suggest that the target of deletion in glioblastoma multiforme includes both p15 and p16 genes. The reason that homozygous deletions, rather than intragenic mutations, are so common in these tumors may be that deletion is a more efficient mechanism for simultaneous inactivation of both genes.
我们运用分子遗传学方法来检测人脑肿瘤中细胞周期抑制基因的状态。我们发现，p16及其邻近基因p15在多形性胶质母细胞瘤中常发生纯合缺失，但在髓母细胞瘤或室管膜瘤中则不然。这种缺失在原发性肿瘤及其衍生的异种移植物中均有发生，但未发现这两个基因中的任何一个有基因内突变。与p16相比，p15基因在正常组织中的表达模式更为广泛，但这两个基因的产物与细胞周期蛋白D依赖性激酶4和6结合的能力相似。这些数据表明，多形性胶质母细胞瘤中缺失的靶点包括p15和p16基因。在这些肿瘤中纯合缺失而非基因内突变如此常见的原因可能是，缺失是使这两个基因同时失活的更有效机制。
