Lemeta Sebsebe, Pylkkänen Lea, Sainio Markku, Niemelä Mika, Saarikoski Sirkku, Husgafvel-Pursiainen Kirsti, Böhling Tom
Department of Pathology, University of Helsinki, Finland.
J Neuropathol Exp Neurol. 2004 Oct;63(10):1072-9. doi: 10.1093/jnen/63.10.1072.
Capillary hemangioblastoma is a benign tumor, occurring sporadically or as a manifestation of von Hippel-Lindau (VHL) disease. Inactivation of the VHL gene at 3p25-26 has been demonstrated in all VHL-associated hemangioblastomas. However, the VHL gene has been found to be inactivated in only 20% to 50% of sporadic tumors. So far, no other gene has been reported to be involved in the development of hemangioblastomas. DNA losses at 6q are frequent alterations in hemangioblastomas, as shown by comparative genomic hybridization. We therefore analyzed 15 hemangioblastomas for loss of heterozygosity (LOH) on chromosome 3p and 6q to reveal the frequency of allelic losses and to determine minimal deleted areas. We detected LOH at 6q for one or more markers in 11 (73%) out of 15 cases (in 9 of 11 sporadic and in 2 of 4 VHL-associated tumors). The analyses revealed a minimal 3-megabase (Mb) deleted region at 6q23-24, where 9 of 11 (82%) informative cases showed LOH. LOH at 3p was seen in 14 out of 15 tumors. LOH occurred concurrently at 6q and 3p in 67% of cases. Our data strongly suggests that a tumor suppressor gene located at 6q23-24 is involved in tumorigenesis of hemangioblastomas, in addition to the VHL gene.
毛细血管性成血管细胞瘤是一种良性肿瘤，可散发性发生或作为冯·希佩尔-林道（VHL）病的一种表现形式。在所有与VHL相关的成血管细胞瘤中均已证实3p25 - 26处的VHL基因失活。然而，仅在20%至50%的散发性肿瘤中发现VHL基因失活。到目前为止，尚未有其他基因被报道参与成血管细胞瘤的发生发展。如比较基因组杂交所示，6q处的DNA缺失是成血管细胞瘤中常见的改变。因此，我们分析了15例成血管细胞瘤在3p和6q染色体上的杂合性缺失（LOH）情况，以揭示等位基因缺失的频率并确定最小缺失区域。我们在15例中的11例（73%）检测到6q处一个或多个标记的LOH（11例散发性肿瘤中的9例以及4例VHL相关肿瘤中的2例）。分析显示在6q23 - 24处有一个最小3兆碱基（Mb）的缺失区域，11例信息丰富的病例中有9例（82%）显示出LOH。15例肿瘤中有14例在3p处出现LOH。67%的病例中6q和3p同时出现LOH。我们的数据强烈表明，除了VHL基因外，位于6q23 - 24的一个肿瘤抑制基因也参与了成血管细胞瘤的肿瘤发生。
