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  • Oncogenomics
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KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression

Oncogene volume 26, pages 158–163 (2007)Cite this article

Abstract

In sporadic colorectal cancer (CRC), KRAS are alternative to BRAF mutations and occur, respectively, in 30 and 10% of cases. Few reports addressed the association between KRAS–BRAF mutations and tumour progression specifically in sporadic microsatellite-stable (MSS) CRC. We screened KRAS and BRAF in 250 MSS primary CRC and 45 lymph node (LN) metastases and analysed the pathological features of the cases to understand the involvement of KRAS–BRAF activation in progression and metastasis. Forty-five per cent of primary MSS CRCs carried mutations in at least one of these genes and mutations were associated with wall invasion (P=0.02), presence and number of LN metastases (P=0.02 and P=0.03, respectively), distant metastases (P=0.004) and advanced stage (P=0.01). We demonstrated that KRAS and BRAF are alternative events in Tis and T1 MSS CRC and, KRAS rather than BRAF mutations, contributed to the progression of MSS CRC. The frequency of KRAS and/or BRAF mutations was higher in LN metastases than in primary carcinomas (P=0.0002). Mutated LN metastases displayed KRAS associated or not with BRAF mutations. BRAF mutations were never present as a single event. Concomitant KRAS and BRAF mutations increased along progression of MSS CRCs, suggesting that activation of both genes is likely to harbour a synergistic effect.

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Acknowledgements

Supported by Grants: Portuguese Fundação para a Ciência e Tecnologia (POCTI/SAU-OBS/56921/2004; REEQ/218/SAL/2005); Novartis- Portugal; Spanish Fondo de Investigaciones Sanitarias (FIS 05/0304); SV, CM, AF and AP were supported by fellowships from the Portuguese Fundação para a Ciência e Tecnologia.

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Authors and Affiliations

  1. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal

    C Oliveira, S Velho, C Moutinho, A Ferreira, A Preto, J C Machado, F Carneiro & R Seruca

  2. Molecular Oncology and Aging Research, Centre d'Investigacions en Bioquimica i Biologia Molecular (CIBBIM), Hospital Universitari Vall d'Hebron, Barcelona, Spain

    E Domingo & S Schwartz Jr

  3. Pathology Department, Hospital de S. João, Porto, Portugal

    A F Capelinha & F Carneiro

  4. INSERM U762 CEPH, INSERM, Paris, France

    A Duval & R Hamelin

  5. Faculty of Medicine, University of Porto, Porto, Portugal

    J C Machado, F Carneiro & R Seruca

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  1. C Oliveira
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Correspondence to R Seruca.

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Oliveira, C., Velho, S., Moutinho, C. et al. KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression. Oncogene 26, 158–163 (2007). https://doi.org/10.1038/sj.onc.1209758

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  • DOI: https://doi.org/10.1038/sj.onc.1209758

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