KRAS codon 12 mutations in Australian non-small cell lung cancer

Background: In certain non-small cell lung cancer (NSCLC) populations, codon 12 mutations of the KRAS oncogene comprising mostly G-T transversions have diagnostic and prognostic value. However, it is not known if these findings are applicable to all populations of lung cancer patients. Aims: To examine for KRAS codon 12 mutations in Australian NSCLC patients. Methods: Tumour samples and corresponding normal lung tissue from 108 Australian patients with NSCLC undergoing curative resection were studied for mutations of KRAS codon 12 using a sensitive PCR assay. Mutations were confirmed by DNA sequencing and correlated with histological subtype, tumour stage, the presence of nodal metastases and survival. Results: Eleven KRAS codon 12 mutations were detected in 108 NSCLCs, with most (8/11) occurring in the adenocarcinoma subtype (17% prevalence), but were not associated with adverse outcome or clinico-pathological features. G-T transversions were surprisingly infrequent (37% of adenocarcinoma mutations). Conclusions: These data add to the evidence suggesting geographical differences in the spectrum and significance of KRAS codon 12 mutational genotypes in NSCLC. While these may be due to genetic variation and/or differences in carcinogen exposure, there is a need for larger population based studies before this potentially important biomarker can be recommended universally for optimising lung cancer management.