机构：[1]Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming650500, Yunnan, P. R. China[2]Faculty of Life Science and Technology, Kunming University of Science andTechnology, Kunming 650500, Yunnan, P. R. China[3]The First People’s Hospital of Yunnan Province, Kunming650031, Yunnan, P. R. China云南省第一人民医院[4]Yunnan Institute of Digestive Disease, The First Affiliated Hospital of KunmingMedical University, Kunming 650032, Yunnan, P. R. China昆明医科大学附属第一医院省级研究所云南省消化疾病研究所
Introduction: KRAS mutations are the most common somatic alterations in colorectal cancer (CRC) patients. Epidermal growth factor receptor (EGFR) antibody therapies are effective in 50% of the CRC patients with wild-type KRAS. To confirm the possible causes of the therapeutic failure, we examined KRAS mutations and analyzed their intratumoral heterogeneity in different areas of the primary tumors and the metastatic liver lesions. Methods: The sequences of exon 2 of KRAS were evaluated by direct sequencing of samples from 26 CRC patients, including 2 patients with colorectal liver metastasis. Tumor tissues were macrodissected from five different areas in primary CRC tumors and two different areas of metastatic liver lesions. Results: KRAS mutations were detected in 26.9% of the primary tumors. By comparing the different areas of primary tumors and liver metastasis, the intratumoral heterogeneity of KRAS mutations was observed in 11.5% of the primary tumors, but not in patients with liver metastasis. This study is the first to report the intratumoral heterogeneity of KRAS mutations in CRC patients from Southwest China, although our relatively small sample size might not provide sufficient statistical power. Conclusions: The failure of EGFR antibody therapies in CRC patients with wild-type KRAS might be attributed to the false-negative sequencing results caused by intratumoral heterogeneity. Considering the high rates of heterogeneity among primary tumors, the different parts of tumors should be tested to correctly predict the KRAS mutations.
基金：
the
Foundation for Innovative Group of the gastrointestinal
surgery of Yunnan Province (No. 2012HC013), the Foundation of Medical
Leading Talent of Yunnan Province (No.
L-201205) and Department of Science and
Technology of Yunnan Province-Kunming
Medical University (NO. 2015FB100). This
research was also partly supported by the
Foundation of Yunnan Institute of Digestive
Disease (No. 2014NS122).
语种：
外文
中科院(CAS)分区：
出版当年[2017]版：
大类|4 区医学
小类|4 区肿瘤学4 区病理学
最新[2023]版：
无
第一作者：
第一作者机构：[1]Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming650500, Yunnan, P. R. China[2]Faculty of Life Science and Technology, Kunming University of Science andTechnology, Kunming 650500, Yunnan, P. R. China[3]The First People’s Hospital of Yunnan Province, Kunming650031, Yunnan, P. R. China
通讯作者：
通讯机构：[2]Faculty of Life Science and Technology, Kunming University of Science andTechnology, Kunming 650500, Yunnan, P. R. China[4]Yunnan Institute of Digestive Disease, The First Affiliated Hospital of KunmingMedical University, Kunming 650032, Yunnan, P. R. China[*1]Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, P. R. China.[*2]Yunnan Institute of Digestive Disease, The First Affliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, P. R. China
推荐引用方式(GB/T 7714)：
Hui-Feng Zhang,Zhen-Rong Xie,Hua-Wei Wang,et al.Intratumoral heterogeneity of KRAS mutations in patients with colorectal cancer and metastatic livers in southwest China[J].International Journal of Clinical and Experimental Pathology.2016,9(2):
APA：
Hui-Feng Zhang,Zhen-Rong Xie,Hua-Wei Wang,Yu Xu,Rui Liang...&Kun-Hua Wang.(2016).Intratumoral heterogeneity of KRAS mutations in patients with colorectal cancer and metastatic livers in southwest China.International Journal of Clinical and Experimental Pathology,9,(2)
MLA：
Hui-Feng Zhang,et al."Intratumoral heterogeneity of KRAS mutations in patients with colorectal cancer and metastatic livers in southwest China".International Journal of Clinical and Experimental Pathology 9..2(2016)
