Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy.

Content Provider	Europe PMC
Author	Di Fiore, F Blanchard, F Charbonnier, F Le Pessot, F Lamy, A Galais, M P Bastit, L Killian, A Sesboüé, R Tuech, J J Queuniet, A M Paillot, B Sabourin, J C Michot, F Michel, P Frebourg, T
Copyright Year	2007
Abstract	The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan–Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.
ISSN	00070920
Journal	British Journal of Cancer
Volume Number	96
PubMed Central reference number	PMC2360149
Issue Number	8
PubMed reference number	17375050
e-ISSN	15321827
DOI	10.1038/sj.bjc.6603685
Language	English
Publisher	Nature Publishing Group
Publisher Date	2007-03-20
Access Restriction	Open
Rights License	This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. Copyright © 2007 Cancer Research UK
Subject Keyword	colorectal cancer EGFR KRAS molecular markers mutation
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology