Characterization of rare transforming KRAS mutations in sporadic colorectal cancer

摘要: KRAS mutational status has been shown to be a predictive biomarker of resistance anti-EGFR monoclonal antibody (mAb) therapy in patients with metastatic colorectal cancer. We report the spectrum mutation 1506 cancer and identification characterization rare insertion mutations within functional domain KRAS. are found 44.5% (670/1506) patients. Two cases harbor double involving both codons 12 13. The frequencies at its 12, 13, 61, 146 75.1%, 19.3%, 2.5%, 2.7%, respectively. most abundant codon is G12D, followed by G12V G12C while G13D predominant Mutations other rare. rate significantly higher women (48%, 296/617) than men (42.1%, 374/889, P = 0.023). Tumors on right colon have frequency those left (57.3% vs. 40.4%, P<0.0001). in-frame affect phosphate-binding loop (codon 10-16) identified. One them never reported before. Compared wild-type protein, variants enhance cellular accumulation active RAS (RAS-GTP) constitutively activate downstream signaling pathway. NIH3T3 cells transfected show enhanced anchorage-independent growth vivo tumorigenicity. Potentially these contribute primary mAb but clinical implication requires further validation.