Beyond KRAS mutation status: influence of KRAScopy number status and microRNAs on clinical outcome to cetuximab in metastatic colorectal cancer patientsReportar como inadecuado




Beyond KRAS mutation status: influence of KRAScopy number status and microRNAs on clinical outcome to cetuximab in metastatic colorectal cancer patients - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Cancer

, 12:292

First Online: 17 July 2012Received: 22 September 2011Accepted: 26 June 2012DOI: 10.1186-1471-2407-12-292

Cite this article as: Mekenkamp, L.J., Tol, J., Dijkstra, J.R. et al. BMC Cancer 2012 12: 292. doi:10.1186-1471-2407-12-292

Abstract

BackgroundKRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor EGFR antibodies in metastatic colorectal cancer mCRC. Novel predictive markers are required to further improve the selection of patients for this treatment. We assessed the influence of modification of KRAS by gene copy number aberration CNA and microRNAs miRNAs in correlation to clinical outcome in mCRC patients treated with cetuximab in combination with chemotherapy and bevacizumab.

MethodsFormalin-fixed paraffin-embedded primary tumour tissue was used from 34 mCRC patients in a phase III trial, who were selected based upon their good n = 17 or poor n = 17 progression-free survival PFS upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab. Gene copy number at the KRAS locus was assessed using high resolution genome-wide array CGH and the expression levels of 17 miRNAs targeting KRAS were determined by real-time PCR.

ResultsCopy number loss of the KRAS locus was observed in the tumour of 5 patients who were all good responders including patients with a KRAS mutation. Copy number gains in two wild-type KRAS tumours were associated with a poor PFS. In KRAS mutated tumours increased miR-200b and decreased miR-143 expression were associated with a good PFS. In wild-type KRAS patients, miRNA expression did not correlate with PFS in a multivariate model.

ConclusionsOur results indicate that the assessment of KRAS CNA and miRNAs targeting KRAS might further optimize the selection of mCRC eligible for anti-EGFR therapy.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-12-292 contains supplementary material, which is available to authorized users.

Leonie JM Mekenkamp, Jolien Tol contributed equally to this work.

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Autor: Leonie JM Mekenkamp - Jolien Tol - Jeroen R Dijkstra - Inge de Krijger - M Elisa Vink-Börger - Shannon van Vliet - Steve

Fuente: https://link.springer.com/







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