Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 罗珮莹女士 (中医中药研究所) |
| 唐红文博士 (病理解剖及细胞学系) |
| 杜家辉教授 (病理解剖及细胞学系) |
| 吴兆文教授 (外科学系) |
| 麦?忠教授 (外科学系) |
| 马碧如教授 (肿瘤学系) |
| 陈永鸿教授 (病理解剖及细胞学系) |
| 康伟教授 (病理解剖及细胞学系) |
| 罗珮莹女士 (中医中药研究所) |
| 冼铭聪先生 (病理解剖及细胞学系) |
| 龙伟明博士 (病理解剖及细胞学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.4161/cbt.28550 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/13WOS source URL
其它资讯
摘要KRAS mutational status has been shown to be a predictive biomarker of resistance to anti-EGFR monoclonal antibody (mAb) therapy in patients with metastatic colorectal cancer. We report the spectrum of KRAS mutation in 1506 patients with colorectal cancer and the identification and characterization of rare insertion mutations within the functional domain of KRAS. KRAS mutations are found in 44.5% (670/1506) of the patients. Two cases are found to harbor double mutations involving both codons 12 and http://aims.cuhk.edu.hk/converis/portal/Publication/13. The frequencies of KRAS mutations at its codons 12, http://aims.cuhk.edu.hk/converis/portal/Publication/13, 61, and 146 are 75.1%, 19.3%, 2.5%, and 2.7%, respectively. The most abundant mutation of codon 12 is G12D, followed by G12V and G12C while Ghttp://aims.cuhk.edu.hk/converis/portal/Publication/13D is the predominant mutation in codon http://aims.cuhk.edu.hk/converis/portal/Publication/13. Mutations in other codons are rare. The KRAS mutation rate is significantly higher in women (48%, 296/617) than in men (42.1%, 374/889, P = 0.023). Tumors on the right colon have a higher frequency of KRAS mutations than those on the left (57.3% vs. 40.4%, P < 0.0001). Two in-frame insertion mutations affect the phosphate-binding loop (codon 10-16) of KRAS are identified. One of them has never been reported before. Compared with wild-type protein, the insertion variants enhance the cellular accumulation of active RAS (RAS-GTP) and constitutively activate the downstream signaling pathway. NIH3T3 cells transfected with the insertion variants show enhanced anchorage-independent growth and in vivo tumorigenicity. Potentially these mutations contribute to primary resistance to anti-EGFR mAb therapy but the clinical implication requires further validation.
着者Tong JHM, Lung RWM, Sin FMC, Law PPY, Kang W, Chan AWH, Ma BBY, Mak TWC, Ng SSM, To KF
期刊名称Cancer Biology and Therapy
出版年份2014
月份6
日期1
卷号15
期次6
出版社Taylor & Francis: STM, Behavioural Science and Public Health Titles
页次768 - 776
国际标準期刊号1538-4047
电子国际标準期刊号1555-8576
语言英式英语
关键词colorectal cancer; KRAS; targeted therapy
Web of Science 学科类别Oncology; ONCOLOGY
