KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer

Jeanne Tie, Lara Lipton, Jayesh Desai, Peter Gibbs, Robert N Jorissen, Michael Christie, Katharine Drummond, Benjamin N J Thomson, Valery Usatoff, Peter Malcolm Evans, Adrian Pick, Simon Knight, Peter Wayne George Carne, Roger Berry, Adrian L Polglase, Paul John McMurrick, Qi Zhao, Dana A Busam, Robert L Strausberg, Enric DomingoIan P Tomlinson, Rachel Midgley, David J Kerr, Oliver M Sieber

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Abstract

Purpose: Oncogene 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 Design: One 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. Results: In 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. Conclusions: KRAS 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
Original languageEnglish
Pages (from-to)1122 - 1130
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number5
DOIs
Publication statusPublished - 2011

Cite this

Tie, J., Lipton, L., Desai, J., Gibbs, P., Jorissen, R. N., Christie, M., Drummond, K., Thomson, B. N. J., Usatoff, V., Evans, P. M., Pick, A., Knight, S., Carne, P. W. G., Berry, R., Polglase, A. L., McMurrick, P. J., Zhao, Q., Busam, D. A., Strausberg, R. L., ... Sieber, O. M. (2011). KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer. Clinical Cancer Research, 17(5), 1122 - 1130. https://doi.org/10.1158/1078-0432.CCR-10-1720