,Genetic and Epigenetic Alterations of DLC-1, a Candidate Tumor Suppressor Gene, in Nasopharyngeal C

• 作 者: Dan PENG Cai-Ping REN Hong-Mei YI Liang ZHOU Xu-Yu YANG Hui LI Kai-Tai YAO
• 机 构: Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha 410078, Ch
• 出 处: 生物化学与生物物理学报（英文版）
• 发表日期: 2006年5期
• 关键词: DLC-1 nasopharyngeal carcinoma hypermethylation loss of heterozygosity

The DLC-1 gene, located at the human chromosome region 8p22, behaves like a tumor suppressor gene and is frequently deleted in diverse tumors. The deletion of 8p22 is not an uncommon event in nasopharyngeal carcinoma (NPC), therefore we explored the expression levels of the DLC-1 gene in NPCs and NPC cell lines by reverse transcription-polymerase chain reaction. The results showed the mRNA level of DLC-1 was downregulated. To identify the mechanism of DLC-1 downregulation in NPC, we investigated the methylation status of the DLC-1 gene using methylation-specific PCR, and found that 79% (31 of 39) of the NPC tissues and two DLC-1 nonexpressing NPC cell lines, 6-10B and 5-8F, were methylated in the DLC-1 CpG island. Microsatellite PCR was also carried out, and loss of heterozygosity was found at four microsatellite sites (D8S552, D8S1754, D8S1790 and D8S549) covering the whole DLC-1 gene with ratios of 33% (4 of 12 informative cases), 18% (2 of 11), 5% (1 of 18), and 25% (3 of 12), respectively. Taken together, our results suggest that DLC-1 might be an NPC-related tumor suppressor gene affected by aberrant promoter methylation and gene deletion.