Joseph Biju, Mamatha Gandra, Raman Gayathree, Shanmugam Mahesh Palanivelu, Kumaramanickavel Govindasamy
Department of Genetics & Molecular Biology, Vision Research Foundation, Chennai, India.
Cancer Biol Ther. 2004 Feb;3(2):184-7. doi: 10.4161/cbt.3.2.620. Epub 2004 Feb 1.
Retinoblastoma can arise due to mutational inactivation or methylation of RB1 gene promoter. A 600-bp CpG island consisting of the essential promoter is present at the 5' end of RB1 gene. Hypermethylation of the CpG island within the RB1 promoter region has been described in unilateral retinoblastoma. In vitro and in vivo studies have suggested that methylation of the RB1 promoter dramatically reduces gene activity. In the present study methylation status of the CpG island within the promoter region of RB1 gene has been evaluated by methylation specific polymerase chain reaction to define the molecular mechanism responsible for retinoblastoma in Indian patients. One unilateral and two bilateral nonhereditary patients had methylation of the RB1 promoter region in which 6.6% of our patients had complete methylation of the RB1 promoter region. This study shows methylation of RB1 promoter is not a major mechanism for retinoblastoma patients in India. Methylation analysis is used in genetic counseling of the family.
视网膜母细胞瘤可因RB1基因启动子的突变失活或甲基化而发生。RB1基因的5'端存在一个由基本启动子组成的600 bp CpG岛。在单侧视网膜母细胞瘤中已发现RB1启动子区域内的CpG岛发生高甲基化。体外和体内研究表明，RB1启动子的甲基化会显著降低基因活性。在本研究中，通过甲基化特异性聚合酶链反应评估了RB1基因启动子区域内CpG岛的甲基化状态，以确定印度患者视网膜母细胞瘤的分子机制。一名单侧和两名双侧非遗传性患者的RB1启动子区域发生甲基化，其中6.6%的患者RB1启动子区域完全甲基化。本研究表明，RB1启动子甲基化不是印度视网膜母细胞瘤患者的主要发病机制。甲基化分析用于该家族的遗传咨询。
