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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Mutation analysis of 13 driver genes of colorectal cancer-related pathways in Taiwanese patients
Yuli Christine Chang, Jan-Gowth Chang, Ta-Chih Liu, Chien-Yu Lin, Shu-Fen Yang, Cheng-Mao Ho, William Tzu-Liang Chen, Ya-Sian Chang
Yuli Christine Chang, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Yuli Christine Chang, Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
Jan-Gowth Chang, Chien-Yu Lin, Shu-Fen Yang, Cheng-Mao Ho, Ya-Sian Chang, Department of Laboratory Medicine, China Medical University Hospital, Taichung 40447, Taiwan
Jan-Gowth Chang, Ya-Sian Chang, Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan
Jan-Gowth Chang, School of Medicine, China Medical University, Taichung 40402, Taiwan
Ta-Chih Liu, Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80707, Taiwan
William Tzu-Liang Chen, Division of Colorectal Surgery, Department of Surgery, China Medical University Hospital, Taichung 40447, Taiwan
Author contributions: Chang YC performed the experiments and drafted the manuscript; Chang JG helped to design the study; Liu TC, Lin CY and Yang SF participated in the statistical analysis; Ho CM helped to design the study; Chen WT participated in the coordination of the study; Chang YS design the study; Chang JG and Chang YS contributed equally to this paper; all authors read and approved the manuscript.
Supported by research grant from the China Medical University Hospital, DMR-103-017.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of the China Medical University Hospital.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ya-Sian Chang, PhD, Epigenome Research Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung 40447, Taiwan.
t25074@mail.cmuh.org.tw
Telephone: +886-4-22052121-2010 Fax: +886-4-22031029
Received: June 14, 2015
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.
