Leuraud P, Marie Y, Robin E, Huguet S, He J, Mokhtari K, Cornu P, Hoang-Xuan K, Sanson M
INSERM U495, Biologie des Interactions Neurone-Glie, Paris, France.
J Neurooncol. 2000 Dec;50(3):207-13. doi: 10.1023/a:1006400723490.
After chromosome 22 and NF2 inactivation, the loss of chromosome 1p is one of the most frequent abnormalities encountered in meningiomas. However the putative tumor suppressor gene located on 1p inactivated in meningiomas has still to be identified. We screened 68 meningiomas for LOH on chromosome 22 and 1. We found 34 LOH on the NF2 region on chromosome 22 (50%) and 19 LOH on 1p (28%), 16 being associated with loss of chromosome 22. Partial deletions delimited a candidate region located between D1S234 and D1S2797. The p18INK4C tumor suppressor gene, a member of the genes family coding for inhibitors of cyclin-dependent kinases, is located in this region. To determine whether p18 is involved in development of meningiomas, we performed a mutation analysis of the p18 gene and a search for homozygous deletion in the 19 meningiomas with 1p loss. Sequencing analysis of the p18 gene revealed one polymorphism, but no somatic mutations and no homozygous deletions were found. These results confirm that the loss of chromosome 1p32 is a frequent feature in meningiomas, however the p18 tumor suppressor gene which is located in this region, does not seem to be involved.
在22号染色体和NF2基因失活后，1号染色体短臂缺失是脑膜瘤中最常见的异常之一。然而，位于1号染色体短臂上、在脑膜瘤中失活的假定肿瘤抑制基因仍有待确定。我们对68例脑膜瘤进行了22号染色体和1号染色体的杂合性缺失（LOH）筛查。我们发现22号染色体上NF2区域有34例LOH（50%），1号染色体短臂有19例LOH（28%），其中16例与22号染色体缺失相关。部分缺失界定了一个位于D1S234和D1S2797之间的候选区域。p18INK4C肿瘤抑制基因是编码细胞周期蛋白依赖性激酶抑制剂的基因家族成员，位于该区域。为了确定p18是否参与脑膜瘤的发生，我们对19例1号染色体短臂缺失的脑膜瘤进行了p18基因的突变分析并寻找纯合缺失。p18基因的测序分析显示一个多态性，但未发现体细胞突变和纯合缺失。这些结果证实1号染色体短臂32区缺失是脑膜瘤的常见特征，然而位于该区域的p18肿瘤抑制基因似乎未参与其中。
