• Jeanne Tie, Lara Lipton, Jayesh Desai, Peter Gibbs, Robert N Jorissen, Michael Christie, Katharine J Drummond, Benjamin N J Thomson, Valery Usatoff, Peter M Evans, Adrian W Pick, Simon Knight, Peter W G Carne, Roger Berry, Adrian Polglase, Paul McMurrick, Qi Zhao, Dana Busam, Robert L Strausberg, Enric Domingo, Ian P M Tomlinson, Rachel Midgley, David Kerr, and Oliver M Sieber.
• Ludwig Colon Cancer Initiative Laboratory, Ludwig Institute for Cancer Research, Parkville, Melbourne, Australia.
• Clin Cancer Res. 2011 Mar 1; 17 (5): 1122-30.

PurposeOncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse.Experimental DesignOne hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. Mutation prevalence was compared between (a) metastases from liver (n = 65), lung (n = 50), and brain (n = 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n = 604). Mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the VICTOR trial.ResultsIn colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: BRAF (3.1%), KRAS (48.4%), NRAS (6.2%), and PIK3CA (16.1%). KRAS mutation prevalence was significantly higher in lung (62.0%) and brain (56.5%) than in liver metastases (32.3%; P = 0.003). Mutation status was highly concordant between primary cancer and metastasis from the same individual. Compared with independent primary cancers, KRAS mutations were more common in lung and brain metastases (P < 0.005), but similar in liver metastases. Correspondingly, KRAS mutation was associated with lung relapse (HR = 2.1; 95% CI, 1.2 to 3.5, P = 0.007) but not liver relapse in patients from the VICTOR trial.ConclusionsKRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. Our data highlight the potential of somatic mutations for informing surveillance strategies.©2011 AACR.

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