Cited by 217Colorectal Cancer Treatments and StudiesGenetic factors in colorectal cancerCancer Genomics and Diagnostics

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KRAS Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer

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Tie, Jeanne, Lipton, Lara, Desai, Jayesh, Gibbs, Peter, Jorissen, Robert N., Christie, Michael, Drummond, Katharine J., Thomson, Benjamin N.J., Usatoff, Valery, Evans, Peter M., Pick, Adrian W., Knight, Simon, Carne, Peter W.G., Berry, Roger, Polglase, Adrian, McMurrick, Paul, Zhao, Qi, Busam, Dana, Strausberg, Robert L., Domingo, Enric, Tomlinson, Ian P.M., Midgley, Rachel, Kerr, David, Sieber, Oliver M.·2011·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-10-1720

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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. Clin Cancer Res; 17(5); 1122–30. ©2011 AACR.

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Authors: Tie, J., Lipton, L., Desai, J., Gibbs, P., Jorissen, R. N., Christie, M., Drummond, K. J., Thomson, B. N. J., Usatoff, V., Evans, P. M., Pick, A. W., Knight, S., Carne, P. W. G., Berry, R., Polglase, A., McMurrick, P., Zhao, Q., Busam, D., Strausberg, R. L., Domingo, E., Tomlinson, I. P. M., Midgley, R., Kerr, D., & Sieber, O. M.
Affiliations: J. Craig Venter Institute (US)
Authors' Affiliations: 1Ludwig Colon Cancer Initiative Laboratory, Ludwig Institute for Cancer Research; 2Faculty of Medicine, Dentistry and Health Sciences, Department of Surgery, University of Melbourne; 3Departments of Medical Oncology, 4Neurosurgery, and 5Surgery, Royal Melbourne Hospital, Parkville; 6Division of Surgical Oncology, Peter MacCallum Cancer Center, East Melbourne; 7Department of Surgery, Western Hospital, Footscray; 8Cabrini Monash University Department of Surgery, St Frances Xavier Cabrini Hospital, Malvern, Melbourne, Australia; 9J. Craig Venter Institute, Rockville, Maryland; 10Ludwig Institute for Cancer Research, New York, New York; 11Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics and 12Department of Clinical Pharmacology, University of Oxford, Oxford, United Kingdom
ORCID: Tie, Jeanne
Lipton, Lara
Desai, Jayesh
Gibbs, Peter
Jorissen, Robert N.
Christie, Michael
Drummond, Katharine J.
Thomson, Benjamin N.J.
Carne, Peter W.G.
Polglase, Adrian
McMurrick, Paul
Zhao, Qi
Domingo, Enric
Tomlinson, Ian P.M.
Sieber, Oliver M.
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2011-03-01
Volume: 17
Issue: 5
Pages: 1122-1130
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-10-1720
OpenAlex: W2038202392
Cited by: 217
References: 50
Citations by year: 2026: 9 · 2025: 4 · 2024: 9 · 2023: 18 · 2022: 7 · 2021: 13 · 2020: 13 · 2019: 17 · 2018: 11 · 2017: 19 · 2016: 15 · 2015: 21 · 2014: 20 · 2013: 16 · 2012: 21
FWCI: 9.60
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords: KRAS mutation, colorectal cancer, lung metastasis, liver metastasis, brain metastases, oncogenic mutations, BRAF, NRAS, PIK3CA, curative resection, somatic mutations, surveillance strategy
MeSH terms: Brain Neoplasms, Colonic Neoplasms, Female, Humans, Liver Neoplasms, Lung Neoplasms, Male, Mutation, Neoplasm Recurrence, Local, Proto-Oncogene Proteins, Genes, ras, Biomarkers, Tumor, Proto-Oncogene Proteins p21(ras), ras Proteins, Phosphatidylinositol 3-Kinases, Gene Expression Profiling, Proto-Oncogene Proteins B-raf, Microsatellite Instability, Class I Phosphatidylinositol 3-Kinases

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KRAS Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer

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