Molecular and Genetic Medicine

APC, FBXW7, KRAS, PIK3CA, and TP53 Gene Mutations in Human Colorectal Cancer Tumors Frequently Detected by Next-Generation DNA Sequencing

Abstract

Zheng Xu Cai, Xu Dong Tang, He Li Gao, Chuanning Tang, Vijayalakshmi Nandakumar, Lindsey Jones, Hua Ye, Feng Lou, Dandan Zhang, Hong Sun, Haichao Dong, Guangchun Zhang, Zhiyuan Liu, Zhishou Dong, Baishuai Guo, He Yan, Chaowei Yan, Lu Wang, Ziyi Su, Feng Yun Wang, Jia Jia Wan, Feng Qi Fang, Hai Long Chen, Dong Shang, Xue F Huang, Si-Yi Chen and and Hui S

Colorectal cancer (CRC) is the fourth leading cause of cancer deaths worldwide. Genetic mutations have been linked to 5-10% of CRCs, with other environmental, genetic, and epigenetic factors influencing development and progression of the cancer. As individual cancers exhibit unique mutation patterns, identification of the distinctive CRC profile is essential to develop more effective target therapies. In this study, we used Ion Torrent Ampliseq Cancer Panel to sequence 737 loci from 45 cancer-related genes to identify genetic mutations in 93 human colorectal cancer samples. Sequencing analysis revealed frequent missense mutations in APC (17.2%), FBXW7 (10.8%), KRAS (50.5%), PIK3CA (10.8%), and TP53 (23.7%) in CRC samples of various histologic types, and additional mutations were also detected in other genes (BRAF, CTNNB1, NRAS, and SMAD4) at lesser frequencies. We also found common combination mutations between KRAS and TP53 (12.9%), KRAS and APC (8.6%), and KRAS and PIK3CA (8.6%). Sequencing individual human cancers may be the key to developing more effective drugs to target individual, cancer-specific mutations. Identifying the complete mutation profile in CRCs for the application of personalized and tailored targeted therapy is critical for developing new cancer treatments. We believe a faster and cost effective genotyping tool such as Ion Torrent sequencing technology will be greatly beneficial for the assignment of such specific therapeutics for CRCs in the near future.