KRAS CODON-12 MUTATIONS IN AUSTRALIAN NONSMALL CELL LUNG-CANCER

Background: In certain non-small cell lung cancer (NSCLC) populations, codon 12 mutations of the KRAS oncogene comprising mostly G-T transve rsions have diagnostic and prognostic value. However, it is not known if these findings are applicable to all populations of lung cancer pat ients. Aims: To examine for KRAS codon 12 mutations in Australian NSCL C patients. Methods: Tumour samples and corresponding normal lung tiss ue from 108 Australian patients with NSCLC undergoing curative resecti on were studied for mutations of KRAS codon 12 using a sensitive PCR a ssay. Mutations were confirmed by DNA sequencing and correlated with h istological subtype, tumour stage, the presence of nodal metastases an d survival. Results: Eleven KRAS codon 12 mutations were detected in 1 08 NSCLCs, with most (8/11) occurring in the adenocarcinoma subtype (1 7% prevalence), but were not associated with adverse outcome or clinic o-pathological features. G-T transversions were surprisingly infrequen t (37% of adenocarcinoma mutations). Conclusions: These data add to th e evidence suggesting geographical differences in the spectrum and sig nificance of KRAS codon 12 mutational genotypes in NSCLC. While these may be due to genetic variation and/or differences in carcinogen expos ure, there is a need for larger population based studies before this p otentially important biomarker can be recommended universally for opti mising lung cancer management.