Chang Yuli Christine, Chang Jan-Gowth, Liu Ta-Chih, Lin Chien-Yu, Yang Shu-Fen, Ho Cheng-Mao, Chen William Tzu-Liang, Chang Ya-Sian
Yuli Christine Chang, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
World J Gastroenterol. 2016 Feb 21;22(7):2314-25. doi: 10.3748/wjg.v22.i7.2314.
To investigate the driver gene mutations associated with colorectal cancer (CRC) in the Taiwanese population.
In this study, 103 patients with CRC were evaluated. The samples consisted of 66 men and 37 women with a median age of 59 years and an age range of 26-86 years. We used high-resolution melting analysis (HRM) and direct DNA sequencing to characterize the mutations in 13 driver genes of CRC-related pathways. The HRM assays were conducted using the LightCycler® 480 Instrument provided with the software LightCycler® 480 Gene Scanning Software Version 1.5. We also compared the clinicopathological data of CRC patients with the driver gene mutation status.
Of the 103 patients evaluated, 73.79% had mutations in one of the 13 driver genes. We discovered 18 novel mutations in APC, MLH1, MSH2, PMS2, SMAD4 and TP53 that have not been previously reported. Additionally, we found 16 de novo mutations in APC, BMPR1A, MLH1, MSH2, MSH6, MUTYH and PMS2 in cancerous tissues previously reported in the dbSNP database; however, these mutations could not be detected in peripheral blood cells. The APC mutation correlates with lymph node metastasis (34.69% vs 12.96%, P = 0.009) and cancer stage (34.78% vs 14.04%, P = 0.013). No association was observed between other driver gene mutations and clinicopathological features. Furthermore, having two or more driver gene mutations correlates with the degree of lymph node metastasis (42.86% vs 24.07%, P = 0.043).
Our findings confirm the importance of 13 CRC-related pathway driver genes in the development of CRC in Taiwanese patients.
研究台湾人群中与结直肠癌（CRC）相关的驱动基因突变。
本研究评估了103例CRC患者。样本包括66名男性和37名女性，中位年龄为59岁，年龄范围为26 - 86岁。我们使用高分辨率熔解分析（HRM）和直接DNA测序来鉴定CRC相关通路的13个驱动基因中的突变。HRM分析使用配备LightCycler® 480基因扫描软件版本1.5的LightCycler® 480仪器进行。我们还比较了CRC患者的临床病理数据与驱动基因突变状态。
在评估的103例患者中，73.79%在13个驱动基因中的一个发生了突变。我们在APC、MLH1、MSH2、PMS2、SMAD4和TP53中发现了18个先前未报道的新突变。此外，我们在dbSNP数据库中先前报道的癌组织中的APC、BMPR1A、MLH1、MSH2、MSH6、MUTYH和PMS2中发现了16个新发突变；然而，这些突变在外周血细胞中未被检测到。APC突变与淋巴结转移相关（34.69%对12.96%，P = 0.009）和癌症分期相关（34.78%对14.04%，P = 0.013）。未观察到其他驱动基因突变与临床病理特征之间的关联。此外，有两个或更多驱动基因突变与淋巴结转移程度相关（42.86%对24.07%，P = 0.043）。
我们的研究结果证实了13个CRC相关通路驱动基因在台湾患者CRC发生中的重要性。
