Mutation analysis of 13 driver genes of colorectalcancer-related pathways in Taiwan Residents patients

AIM To investigate the driver gene mutations associatedwith colorectal cancer （CRC） in the Taiwan Residentspopulation.METHODS： In this study, 103 patients with CRCwere evaluated. The samples consisted of 66 menand 37 women with a median age of 59 years and anage range of 26-86 years. We used high-resolutionmelting analysis （HRM） and direct DNA sequencing tocharacterize the mutations in 13 driver genes of CRCrelatedpathways. The HRM assays were conductedusing the LightCycler？ 480 Instrument provided with the software LightCycler 480 Gene Scanning SoftwareVersion 1.5. We also compared the clinicopathologicaldata of CRC patients with the driver gene mutationstatus.RESULTS： Of the 103 patients evaluated, 73.79%had mutations in one of the 13 driver genes. Wediscovered 18 novel mutations in APC , MLH1 , MSH2 ,PMS2 , SMAD4 and TP53 that have not been previouslyreported. Additionally, we found 16 de novo mutationsin APC , BMPR1A , MLH1 , MSH2 , MSH6 , MUTYH andPMS2 in cancerous tissues previously reported in thedbSNP database; however, these mutations couldnot be detected in peripheral blood cells. The APCmutation 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 wasobserved between other driver gene mutations andclinicopathological features. Furthermore, having twoor more driver gene mutations correlates with thedegree of lymph node metastasis （42.86% vs 24.07%,P = 0.043）.CONCLUSION： Our findings confirm the importanceof 13 CRC-related pathway driver genes in the developmentof CRC in Taiwan Residents patients.