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KRAS Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer
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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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“although RAS mutations have been associated with increased tendency for lung involvement in colorectal cancer (33–35).”
From Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRAS G12C-Mutated Metastatic Colorectal Cancer (2024) · cites this paper as [34]
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Cites
Gentleman R: R: A language for data analysis and graphics
Ihaka, R., & Gentleman, R. (1996) · Journal of Computational and Graphical Statistics · doi:10.1080/10618600.1996.10474713 · Cited by 11,747
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20006 · Cited by 9,709
Genetic Alterations during Colorectal-Tumor Development
Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Preisinger, A. C., Leppert, M., de Vries-Smits, A. M. M., & Bos, J. L. (1988) · New England Journal of Medicine · doi:10.1056/nejm198809013190901 · Cited by 6,809
R: A Language for Data Analysis and Graphics
Ihaka, R., & Gentleman, R. C. (1996) · Journal of Computational and Graphical Statistics · doi:10.2307/1390807 · Cited by 4,245
K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer
Karapetis, C. S., Khambata-Ford, S., Jonker, D. J., O'Callaghan, C. J., Tu, D., Tebbutt, N. C., Simes, R. J., Chalchal, H., Shapiro, J. D., Robitaille, S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804385 · Cited by 3,622
High Frequency of Mutations of the PIK3CA Gene in Human Cancers
Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A. F., Powell, S. M., Riggins, G. J., et al. (2004) · Science · doi:10.1126/science.1096502 · Cited by 3,448
Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer
Amado, R. G., Wolf, M., Peeters, M., Van Cutsem, E., Siena, S., Freeman, D. J., Juan, T., Sikorski, R., Suggs, S., Radinsky, R., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.7116 · Cited by 3,207
A census of human cancer genes
Futreal, P. A., Coin, L., Marshall, M., Down, T., Hubbard, T., Wooster, R., Rahman, N., & Stratton, M. R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1299 · Cited by 3,184
KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer
Lièvre, A., Bachet, J.-B., Le Corre, D., Boige, V., Landi, B., Emile, J.-F., Côté, J.-F., Tomasic, G., Penna, C., Ducreux, M., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0191 · Cited by 2,229
Prevalence of ras gene mutations in human colorectal cancers
Bos, J. L., Fearon, E. R., Hamilton, S. R., Vries, M. V., BOOM, J. H. V., van der Eb, A. J., & Vogelstein, B. (1987) · Nature · doi:10.1038/327293a0 · Cited by 1,860
Wild-Type BRAF Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer
Di Nicolantonio, F., Martini, M., Molinari, F., Sartore-Bianchi, A., Arena, S., Saletti, P., De Dosso, S., Mazzucchelli, L., Frattini, M., Siena, S., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.0786 · Cited by 1,591
Tumor Microsatellite Instability and Clinical Outcome in Young Patients with Colorectal Cancer
Gryfe, R., Kim, H., Hsieh, E., Aronson, M. D., Holowaty, E. J., Bull, S. B., Redston, M. S., & Gallinger, S. (2000) · New England Journal of Medicine · doi:10.1056/nejm200001133420201 · Cited by 1,396
RAF/RAS oncogenes and mismatch-repair status
Rajagopalan, H., Bardelli, A., Lengauer, C., Kinzler, K. W., Vogelstein, B., & Velculescu, V. E. (2002) · Nature · doi:10.1038/418934a · Cited by 1,224
Rodrı́guez-Bigas, M. A., Boland, C. R., Hamilton, S. R., Henson, D. E., Srivastava, S., Jass, J. R., Khan, P. M., Lynch, H. T., Smyrk, T. C., Perucho, M., et al. (1997) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/89.23.1758 · Cited by 1,136
Detection of high incidence of K-ras oncogenes during human colon tumorigenesis
Forrester, K., Almoguera, C., Han, K., Grizzle, W. E., & Perucho, M. (1987) · Nature · doi:10.1038/327298a0 · Cited by 1,061
High-throughput oncogene mutation profiling in human cancer
Thomas, R. K., Baker, A. C., Debiasi, R. M., Winckler, W., LaFramboise, T., Lin, W. M., Wang, M., Feng, W., Zander, T., MacConaill, L. E., et al. (2007) · Nature Genetics · doi:10.1038/ng1975 · Cited by 978
Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study
Andreyev, J. N., Norman, A. R., Cunningham, D., Oates, J. R., Dix, B. R., Iacopetta, B. J., Young, J. P., Walsh, T. P., Ward, R. L., Hawkins, N., et al. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1964 · Cited by 880
Ogino, S., Nosho, K., Kirkner, G. J., Kawasaki, T., Meyerhardt, J. A., Loda, M. F., Giovannucci, E. L., & Fuchs, C. S. (2008) · Gut · doi:10.1136/gut.2008.155473 · Cited by 772
Sartore-Bianchi, A., Martini, M., Molinari, F., Veronese, S., Nichelatti, M., Artale, S., Di Nicolantonio, F., Saletti, P., De Dosso, S., Mazzucchelli, L., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2466 · Cited by 739
Renehan, A. G., Egger, M., Saunders, M. P., & O'Dwyer, S. T. (2002) · BMJ · doi:10.1136/bmj.324.7341.813 · Cited by 651
Desch, C. E., Benson, A. B., Somerfield, M. R., Flynn, P. J., Krause, C., Loprinzi, C. L., Minsky, B. D., Pfister, D. G., Virgo, K. S., & Petrelli, N. J. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.0063 · Cited by 558
Pfannschmidt, J., Dienemann, H., & Hoffmann, H. (2007) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2007.02.093 · Cited by 555
Jhawer, M., Goel, S., Wilson, A. J., Montagna, C., Ling, Y.-H., Byun, D.-S., Nasser, S., Arango, D., Shin, J., Klampfer, L., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5659 · Cited by 460
BRAF Mutation in Metastatic Colorectal Cancer
Tol, J., Nagtegaal, I. D., & Punt, C. J. A. (2009) · New England Journal of Medicine · doi:10.1056/nejmc0904160 · Cited by 445
Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples
MacConaill, L. E., Campbell, C. D., Kehoe, S. M., Bass, A. J., Hatton, C., Niu, L., Davis, M., Yao, K., Hanna, M., Mondal, C., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007887 · Cited by 436
Yuen, S. T., Davies, H. R., Chan, T. L., Ho, J. W. C., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Tsui, W. W., Chan, A. S. Y., et al. (2002) · PubMed · Cited by 404
Follow-up of patients with curatively resected colorectal cancer: a practice guideline
Figueredo, A., Rumble, R. B., Maroun, J., Earle, C. C., Cummings, B., McLeod, R., Zuraw, L., Zwaal, C., & the members of the Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care (2003) · BMC Cancer · doi:10.1186/1471-2407-3-26 · Cited by 392
The prevalence of PIK3CA mutations in gastric and colon cancer
Velho, S., Oliveíra, C., Ferreira, A. M., Ferreira, A. C., Suriano, G., Schwartz, S., Duval, A., Carneiro, F., Machado, J. C., Hamelin, R., et al. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.04.022 · Cited by 342
Follow-Up After Curative Resection of Colorectal Cancer: A Meta-Analysis
Tjandra, J. J., & Chan, M. K. Y. (2007) · Diseases of the Colon & Rectum · doi:10.1007/s10350-007-9030-5 · Cited by 342
Survival after hepatic resection in metastatic colorectal cancer
Cummings, L. C., Payes, J. D., & Cooper, G. S. (2007) · Cancer · doi:10.1002/cncr.22448 · Cited by 336
Samowitz, W. S., Curtin, K. P., Schaffer, D., Robertson, M. A., Leppert, M., & Slattery, M. L. (2000) · PubMed · Cited by 320
Manfrédi, S., Bouvier, A., Lepage, C., Hatem, C., Dancourt, V., & Faivre, J. (2006) · British journal of surgery · doi:10.1002/bjs.5349 · Cited by 316
Prenen, H., De Schutter, J., Jacobs, B., De Roock, W., Biesmans, B., Claes, B., Lambrechts, D., Van Cutsem, E., & Tejpar, S. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2961 · Cited by 291
Aggressive cutaneous malignancies following cardiothoracic transplantation
Veness, M., Quinn, D. I., Ong, C. S., KEOGH, A. M., Macdonald, P. S., Cooper, S. G., & Morgan, G. W. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990415)85:8 · Cited by 213
Follow-up of patients with colorectal cancer
Kievit, J. (2002) · European Journal of Cancer · doi:10.1016/s0959-8049(02)00061-8 · Cited by 206
Mutations of KRAS and BRAF in Primary and Matched Metastatic Sites of Colorectal Cancer
Artale, S., Sartore-Bianchi, A., Veronese, S. M., Gambi, V., Sarnataro, C. S., Gambacorta, M., Lauricella, C., & Siena, S. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.7286 · Cited by 192
Nash, G. M., Gimbel, M., Shia, J., Nathanson, D. R., Ndubuisi, M. I., Zeng, Z.-S., Kemeny, N., & Paty, P. B. (2010) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0605-3 · Cited by 172
Cejas, P., López-Gómez, M., Aguayo, C., Madero, R., de Castro, J., Belda-Iniesta, C., Barriuso, J., Moreno, V., Larrauri, J., López, R., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008199 · Cited by 154
Étienne-Grimaldi, M.-C., Formento, J., Francoual, M., François, É., Formento, P., Renée, N., Laurent‐Puig, P., Chazal, M., Benchimol, D., Delpéro, J., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4906 · Cited by 151
Colorectal carcinoma and brain metastasis: Distribution, treatment, and survival
Hammound, M. A., McCutcheon, I. E., Elsouki, R., Schoppa, D., & Patt, Y. Z. (1996) · Annals of Surgical Oncology · doi:10.1007/bf02305763 · Cited by 148
Al‐Mulla, F., Going, J. J., Sowden, E., Winter, A., Pickford, I. R., & Birnie, G. D. (1998) · The Journal of Pathology · doi:10.1002/(sici)1096-9896(199806)185:2 · Cited by 122
Oudejans, J. J., Slebos, R. J. C., Zoetmulder, F. A. N., Mooi, W. J., & Rodenhuis, S. (1991) · International Journal of Cancer · doi:10.1002/ijc.2910490613 · Cited by 100
Lurkin, I., Stoehr, R., Hurst, C. D., van Tilborg, A. A. G., Knowles, M. A., Hartmann, A., & Zwarthoff, E. C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008802 · Cited by 94
Kjeldsen, B. J., Kronborg, O., Fenger, C., & Jørgensen, O. D. (1997) · International Journal of Colorectal Disease · doi:10.1007/s003840050118 · Cited by 88
Primary colon cancer: ESMO Clinical Recommendations for diagnosis, adjuvant treatment and follow-up
Cutsem, E. V., & Oliveira, J. (2009) · Annals of Oncology · doi:10.1093/annonc/mdp126 · Cited by 79
Wang, C., van Rijnsoever, M., Grieu, F., Bydder, S. A., Elsaleh, H., Joseph, D. J., Harvey, J. M., & Iacopetta, B. J. (2003) · Oncology · doi:10.1159/000069311 · Cited by 65
Zauber, P., Sabbath-Solitare, M., Marotta, S. P., & Bishop, D. T. (2003) · Molecular Pathology · doi:10.1136/mp.56.3.137 · Cited by 60
Markopoulos, C. J., Polychronis, A., Dafni, U. G., Koukouras, D., Zobolas, V., Tzorakoleftherakis, E., Xepapadakis, G., & Gogas, H. J. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn545 · Cited by 50
Aprile, G., Zanon, E., Tuniz, F., Iaiza, E., Pauli, F. D., Pella, N., Pizzolitto, S., Buffoli, A., Piga, A., Škrap, M., et al. (2008) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-008-0468-1 · Cited by 47
Colorectal Cancer: Surveillance
Dujovny, N., & Hourigan, J. S. (2011) · Springer eBooks · doi:10.1007/978-1-4419-1584-9_48 · Cited by 42
A Trial of Adjuvant Therapy in Colorectal Cancer: The VICTOR Trial
Pendlebury, S., Duchesne, F., Reed, K. A., Smith, J. L., & Kerr, D. J. (2003) · Clinical Colorectal Cancer · doi:10.3816/ccc.2003.n.013 · Cited by 18
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Metadata
- 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
- Venue
- Clinical Cancer Research
- Published
- 2011-03-01
- Volume
- 17
- Issue
- 5
- Pages
- 1122-1130
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- 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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