Rousseau E, Ruchoux M-M, Scaravilli F, Chapon F, Vinchon M, De Smet C, Godfraind C, Vikkula M
Laboratory of Neuropathology, Université Catholique de Louvain, Brussels, Belgium.
Neuropathol Appl Neurobiol. 2003 Dec;29(6):574-83. doi: 10.1046/j.0305-1846.2003.00505.x.
Ependymal tumours are histologically and clinically varied lesions. Numerical abnormalities of chromosome 9 are frequently associated with these tumours. Nevertheless, the three important tumour suppressor genes located in this chromosome, CDKN2A, CDKN2B and p14 ARF, have not been reported to be commonly altered in them. We studied promoter methylation of these genes, an important mechanism associated with gene silencing in a series of 152 ependymal tumours of WHO grades I to III. Methylation status of the CDKN2A, CDKN2B and p14 ARF promoters was assessed by methylation-specific polymerase chain reaction and the genetic results were correlated to clinicopathological features. We observed promoter methylation for CDKN2A in 21% (26/123) of tumours, for CDKN2B in 32% (23/71) and p14 ARF in 21% (23/108). For all three genes, posterior fossa ependymomas were less frequently methylated in paediatric patients than in adults. For CDKN2B, extracranial tumours were more frequently methylated than intracranial ones. For CDKN2B and p14 ARF, methylation was more frequent in low-grade tumours; the reverse was observed for CDKN2A. CDKN2A, CDKN2B and p14 ARF promoters were methylated in 21-32% of the tumours. Frequencies of methylation varied according to clinicopathological features. This suggests a role for these genes in ependymoma tumorigenesis.
室管膜瘤是组织学和临床特征各异的病变。9号染色体的数目异常常与这些肿瘤相关。然而，位于该染色体上的三个重要肿瘤抑制基因CDKN2A、CDKN2B和p14 ARF，尚未报道在这些肿瘤中普遍发生改变。我们研究了这些基因的启动子甲基化情况，这是一种与基因沉默相关的重要机制，研究对象为152例世界卫生组织I至III级的室管膜瘤。通过甲基化特异性聚合酶链反应评估CDKN2A、CDKN2B和p14 ARF启动子的甲基化状态，并将基因检测结果与临床病理特征相关联。我们观察到，21%（26/123）的肿瘤中CDKN2A启动子发生甲基化，32%（23/71）的肿瘤中CDKN2B启动子发生甲基化，21%（23/108）的肿瘤中p14 ARF启动子发生甲基化。对于所有这三个基因，小儿后颅窝室管膜瘤的甲基化频率低于成人。对于CDKN2B，颅外肿瘤的甲基化频率高于颅内肿瘤。对于CDKN2B和p14 ARF，低级别肿瘤中的甲基化更为常见；而CDKN2A则相反。21%-32%的肿瘤中CDKN2A、CDKN2B和p14 ARF启动子发生甲基化。甲基化频率因临床病理特征而异。这表明这些基因在室管膜瘤的肿瘤发生过程中发挥作用。
