Published online Feb 21, 2016. doi: 10.3748/wjg.v22.i7.2314
Peer-review started: June 15, 2015
First decision: October 14, 2015
Revised: October 28, 2015
Accepted: November 30, 2015
Article in press: November 30, 2015
Published online: February 21, 2016
Processing time: 231 Days and 2.4 Hours
AIM: To investigate the driver gene mutations associated with colorectal cancer (CRC) in the Taiwanese population.
METHODS: 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.
RESULTS: 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).
CONCLUSION: Our findings confirm the importance of 13 CRC-related pathway driver genes in the development of CRC in Taiwanese patients.
Core tip: In Taiwan, colorectal cancer (CRC) has had the highest incidences among cancers recently. In a study of 103 patients with CRC, we identified 18 novel mutations in APC, MLH1, MSH2, PMS2, SMAD4 and TP53. We assessed the frequency of non-pathological somatic mutations during oncogenesis, which has not been explored before. Our results indicated 16 de novo mutations that have been previously described in a public database and were detected in cancerous tissues only, but not in the patient’s blood cells. We suggest these mutation sites may belong to a frequent mutational hotspot in both germline and cancerous tissues.