%0 Journal Article
%T Beyond KRAS mutation status: influence of KRAS copy number status and microRNAs on clinical outcome to cetuximab in metastatic colorectal cancer patients
%A Leonie J.M. Mekenkamp
%A Jolien Tol
%A Jeroen R. Dijkstra
%A Inge de Krijger
%A Elisa Vink-Borger
%A Steven Teerenstra
%A Eveline Kamping
%A Eugene Verwiel
%A Miriam Koopman
%A Gerrit A. Meijer
%A Han J.M. van Krieken
%A Roland Kuiper
%A Cornelis J.A. Punt
%A Iris D. Nagtegaal
%A Shannon van Vliet
%J BMC Cancer
%D 2012
%I BioMed Central
%R 10.1186/1471-2407-12-292
%X Formalin-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.Copy 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.Our results indicate that the assessment of KRAS CNA and miRNAs targeting KRAS might further optimize the selection of mCRC eligible for anti-EGFR therapy.
%U http://www.biomedcentral.com/1471-2407/12/292/abstract