Furonaka Osamu, Takeshima Yukio, Awaya Hirokazu, Ishida Hajime, Kohno Nobuoki, Inai Kouki
Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Pathol Int. 2004 Aug;54(8):549-55. doi: 10.1111/j.1440-1827.2004.01663.x.
Aberrant methylation of cytosines in CpG islands of the promoter regions of tumor suppressor genes is found in human tumors as a common mechanism of gene silencing. We investigated the methylation status of the chromosome 9p21 gene cluster (p14(ARF), p15(INK4b) and p16(INK4a) genes) by methylation-specific polymerase chain reaction in 20 central and 40 peripheral types of pulmonary squamous cell carcinoma (SqCC) in order to determine the differences between the pathogeneses of the central and peripheral types of SqCC. The frequencies of methylation were 30% for the p14(ARF) gene, 20% for the p15(INK4b) gene and 40% for the p16(INK4a) gene in the central type and 25% for the p14(ARF) gene, 10% for the p15(INK4b) gene and 38% for the p16(INK4a) gene in the peripheral type. Cases in which there was methylation of the p16(INK4a) gene had a higher smoking index in the peripheral type (P = 0.007). This trend was not detected in the central type. Methylation of two or three genes was observed in 55% of methylation in at least one gene of the central type but in only 17% of the peripheral type. This overlap methylation of the chromosome 9p21 gene cluster was found more frequently in the central type (P = 0.02). These findings suggest one of the epigenetic differences between the central and peripheral types of SqCC.
在人类肿瘤中，抑癌基因启动子区域CpG岛中的胞嘧啶异常甲基化是一种常见的基因沉默机制。我们通过甲基化特异性聚合酶链反应，研究了20例中央型和40例周围型肺鳞状细胞癌（SqCC）中9号染色体p21基因簇（p14(ARF)、p15(INK4b)和p16(INK4a)基因）的甲基化状态，以确定中央型和周围型SqCC发病机制之间的差异。中央型中，p14(ARF)基因的甲基化频率为30%，p15(INK4b)基因的甲基化频率为20%，p16(INK4a)基因的甲基化频率为40%；周围型中，p14(ARF)基因的甲基化频率为25%，p15(INK4b)基因的甲基化频率为10%，p16(INK4a)基因的甲基化频率为38%。在周围型中，p16(INK4a)基因发生甲基化的病例吸烟指数较高（P = 0.007）。在中央型中未检测到这种趋势。在中央型中，至少一个基因发生甲基化的病例中，55%观察到两个或三个基因的甲基化，但在周围型中仅为17%。9号染色体p21基因簇的这种重叠甲基化在中央型中更常见（P = 0.02）。这些发现提示了中央型和周围型SqCC之间的一种表观遗传学差异。
