Martinez-Delgado B, Robledo M, Arranz E, Osorio A, García M J, Echezarreta G, Rivas C, Benitez J
Genetic Department, Fundacion Jimenez Diaz, Madrid, Spain.
Leukemia. 1998 Jun;12(6):937-41. doi: 10.1038/sj.leu.2401009.
P15 (MTS2) gene is a candidate tumor suppressor gene localized adjacent to the p16 gene at 9p21. Deletions at the 9p21 region frequently affect both p16 and p15 genes, however, mutations in the coding sequence of the p15 gene have not been found in the majority of tumors analyzed, including non-Hodgkin's lymphomas. Abnormal methylation of the promoter region of p15 has been recently described as an alternative mechanism of inactivation of this gene. We analyzed 72 non-Hodgkin's lymphomas (NHL) for methylation at p15 exon 1 by PCR and Southern blot techniques using methylation-sensitive restriction enzymes. Abnormal methylation was found in eight cases (11%), most of them (three MALT, one anaplastic T cell lymphoma, one Burkitt and one follicular lymphoma) showing hypermethylation in the p16 gene also. In contrast, two pleomorphic T cell NHL showed a selective methylation at p15 gene, while the p16 gene remained unmethylated. The results show that methylation at the p15 gene is frequently associated with p16 methylation in NHL, and suggest that selective methylation of p15, although uncommon, could be a specific alteration implicated in T cell NHL.
P15（MTS2）基因是一种候选肿瘤抑制基因，定位于9号染色体短臂21区（9p21），与p16基因相邻。9p21区域的缺失常常同时影响p16和p15基因，然而，在包括非霍奇金淋巴瘤在内的大多数分析肿瘤中，尚未发现p15基因编码序列的突变。最近，p15基因启动子区域的异常甲基化被描述为该基因失活的另一种机制。我们使用甲基化敏感限制性内切酶，通过聚合酶链反应（PCR）和Southern印迹技术分析了72例非霍奇金淋巴瘤（NHL）中p15基因外显子1的甲基化情况。在8例（11%）病例中发现了异常甲基化，其中大多数病例（3例黏膜相关淋巴组织淋巴瘤、1例间变性T细胞淋巴瘤、1例伯基特淋巴瘤和1例滤泡性淋巴瘤）在p16基因中也显示出高甲基化。相反，2例多形性T细胞NHL在p15基因处表现出选择性甲基化，而p16基因保持未甲基化状态。结果表明，在NHL中，p15基因的甲基化常常与p16基因的甲基化相关，并且提示p15基因的选择性甲基化虽然不常见，但可能是与T细胞NHL相关的一种特异性改变。
