KRAS Codon 12, 13, 61 and 146 Mutations in 1267 Colorectal Cancers: Clinicopathological, Molecular, and Survival Analyses
Xiaoyun Liao, Yu Imamura, Shuji Ogino. Dana-Farber Cancer Institute, Boston, MA; Brigham and Women's Hospital, Boston, MA
Background: KRAS mutations status is increasingly important for management of colorectal cancer patients. KRAS mutations typically occur in codons 12, 13, 61 and 146. There has been no large-scale study which has comprehensively examined clinicopathologic, molecular, and prognostic associations of KRAS codon 61 and 146 mutations in colorectal cancer.
Design: We performed PCR and pyrosequencing of KRAS codons 12, 13, 61 and 146 in 1267 colorectal cancers. We characterized other molecular features [BRAF and PIK3CA mutations; MGMT promoter methylation and loss of expression; microsatellite instability (MSI) status] Proportional hazards model was used to compute mortality hazard ratio (HR) and 95% confidence interval (CI), adjusting for potential confounders, including stage, BRAF mutations, and MSI.
Results: We found 505 (40% of 1267) KRAS-mutated colorectal cancers, including 19 cases (1.5%) in codon 61 mutations, 40 cases (3.2%) in codon 146 mutations, and 12 cases (0.9%) with two or more KRAS mutations.
|Codon||No.||Proportion in 1267 tumors|