Predominance of G to A codon 12 mutation K-ras gene in Dukes' B colorectal cancer

Zulhabri O, Rahman J, Ismail S, Isa MR, Wan Zurinah WN
Correspondence: Dr Zulhabri Othman, zulhabri_othman@yahoo.com

ABSTRACT
Introduction K-ras gene mutations in codons 12 and 13 are one of the earliest events in colon carcinogenesis. 
Methods DNA was extracted from 25 mg of tumour tissue (n = 70) that were taken from tumour mass and pairs with normal epithelial tissue distant from the tumour of colorectal cancer patients. Exon 1 and exon 2 of the K-ras gene were amplified. Hotspot mutations were detected using polymerase chain reaction-based single-strand conformation polymorphism method and confirmed by direct DNA sequencing analysis.
Results Mutations were identified in 14 out of the 70 (20%) colorectal carcinoma tissues. Single-base transition from GGT to GAT (glycine to aspartate) in codon 12 was detected in nine samples, while three samples presented with GGC to GAC transition in codon 13. Patients with large adenoma had a 12-fold higher likelihood of K-ras mutations (odds ratios [OR] 12.31; 95% confidence intervals [CI] 1.81–83.76). Tumours located at the left colon were more likely to present with K-ras mutations (OR 4.54; 95% CI 0.96–21.54). 
Conclusion Our study showed a high frequency of G to A transition of codon 12 mutation of the K-ras gene, withsignificant correlation with tumour size and tumour location.

Keywords: codon 12, colorectal cancer, Dukes’ B, K-ras gene, mutation
Singapore Med J 2012; 53(1): 26–31