Li Jin-Tian, Liu Wei, Kuang Zhi-He, Chen Han-Kui, Li Da-Jiang, Feng Qi-Sheng, Liu Qi-Cai, Hu Bin
Cancer Institute, Cancer Center, Sun Yat-sen Univesity, Guangzhou, 510060, PR China.
Ai Zheng. 2003 Jul;22(7):695-9.
BACKGROUND & OBJECTIVE: Previous study has demonstrated that high frequent gain of 1q was detected in hepatocellular carcinoma (HCC), 1q21-22 was identified as the minimum overlapping amplified region and might contain the candidate oncogenes involved in HCC. RIT1 gene is located in 1q21.3 region and is a member of Ras subfamily. RIT1 protein is similar to Ras protein in molecular structure and functions. It was speculated that RIT1 gene might be a candidate oncogene in HCC. So, the amplification of RIT1 gene was examined in HCC and was linked with the clinical indicators in this study to explore the possible functions of RIT1 gene in HCC development and progression.
The fluorescence quantitative polymerase chain reaction(FQ-PCR) method was established successfully. The number of RIT1 gene DNA copies was examined in the tumor tissues and its paratumor tissues from 43 patients with HCC by PE ABI 7000 Sequence Detector. The ratio of the number of RIT1 gene DNA copies between the tumor tissue and its paratumor tissue represented the extent of amplification of RIT1 gene DNA.
RIT1 gene DNA was amplified in 11 cases (25.6%)among 43 patients. The mean survival time (15 months) of the RIT1 gene-amplification group is significantly shorter than that (34 months) of the non-amplification group (P = 0.0009); furthermore, the pathological grade and the extent of liver cirrhosis were significantly different between the RIT1 gene-amplification group and the non-amplification group (P< 0.01).
The amplification of RIT1 gene might be one of the activation ways in HCC and might play an important role in HCC development and progression.
既往研究表明，在肝细胞癌（HCC）中检测到1q高频扩增，1q21 - 22被确定为最小重叠扩增区域，可能包含与HCC相关的候选癌基因。RIT1基因位于1q21.3区域，是Ras亚家族成员。RIT1蛋白在分子结构和功能上与Ras蛋白相似。推测RIT1基因可能是HCC中的候选癌基因。因此，本研究检测了HCC中RIT1基因的扩增情况，并将其与临床指标相关联，以探讨RIT1基因在HCC发生发展中的可能作用。
成功建立荧光定量聚合酶链反应（FQ-PCR）方法。采用PE ABI 7000序列检测仪检测43例HCC患者肿瘤组织及其癌旁组织中RIT1基因DNA拷贝数。肿瘤组织与癌旁组织中RIT1基因DNA拷贝数的比值代表RIT1基因DNA的扩增程度。
43例患者中11例（25.6%）检测到RIT1基因DNA扩增。RIT1基因扩增组的平均生存时间（15个月）显著短于非扩增组（34个月）（P = 0.0009）；此外，RIT1基因扩增组与非扩增组之间的病理分级和肝硬化程度有显著差异（P<0.01）。
RIT1基因扩增可能是HCC的激活途径之一，可能在HCC的发生发展中起重要作用。
