Khaenam Prasong, Jearanaikoon Patcharee, Pairojkul Chawalit, Bhudhisawasdi Vajarabhongsa, Limpaiboon Temduang
Department of Biomedical Sciences, Graduate School ; Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Exp Ther Med. 2010 Mar;1(2):385-390. doi: 10.3892/etm_00000060. Epub 2010 Mar 1.
The retinoblastoma interacting zinc finger (RIZ1) gene is adjacent to D1S228 where microsatellite instability has been associated with poor patient survival in liver fluke-associated cholangiocarcinoma (CCA). An understanding of the molecular mechanisms underlying the carcinogenesis and pathogenesis of CCA is necessary to improve patient survival. Therefore, we determined the genetic and epigenetic alterations of RIZ1 in 81 CCA samples and 69 matched non-tumor tissues. Methylation was found in 31 of 81 (38%) tumor samples and in 5 of 69 (7%) matched non-tumor tissues. Frameshift mutations (2 of 81) and loss of heterozygosity (LOH) (14 of 81) were not common. Statistical analysis found no significant correlation between RIZ1 alterations and clinicopathological features, but RIZPro704 LOH was associated with patient survival in the multivariate analysis. RIZ1 hypermethylation may be one of the crucial molecular events contributing to cholangiocarcinogenesis, and RIZPro704 LOH may adversely impact patient survival. The biological function of RIZ1 in CCA should be further investigated in order to verify its potential role in regulating this cancer.
视网膜母细胞瘤相互作用锌指（RIZ1）基因与D1S228相邻，在华支睾吸虫相关胆管癌（CCA）中，微卫星不稳定性与患者预后不良相关。了解CCA发生和发病机制的分子机制对于提高患者生存率至关重要。因此，我们测定了81例CCA样本和69例配对的非肿瘤组织中RIZ1的基因和表观遗传改变。在81例肿瘤样本中有31例（38%）发现甲基化，在69例配对的非肿瘤组织中有5例（7%）发现甲基化。移码突变（81例中有2例）和杂合性缺失（LOH）（81例中有14例）并不常见。统计分析发现RIZ1改变与临床病理特征之间无显著相关性，但在多因素分析中RIZPro704 LOH与患者生存率相关。RIZ1高甲基化可能是胆管癌发生的关键分子事件之一，而RIZPro704 LOH可能对患者生存率产生不利影响。应进一步研究RIZ1在CCA中的生物学功能，以验证其在调控这种癌症中的潜在作用。
