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Technical considerations for KRAS testing in colorectal cancer. The biologist’s point of view Volume 96, special issue 4, décembre 2009

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Authors
Inserm, UMR-S775, 75006 Paris, France, Université Paris-Descartes, 75006 Paris, France, Hôpital Européen Georges-Pompidou, Service de biochimie, pôle de biologie, UF de pharmacogénétique et oncologie moléculaire, AP-HP, 75015 Paris, France

Targeted therapy against the EGF receptor was shown to be effective in a subgroup of patients with KRAS wild-type colorectal cancer. Therefore, cetuximab (Erbitux ®) or panitumumab (Vectibix ®) obtained the authorization by the EMEA restricted to patients with KRAS wild-type tumours. KRAS mutational testing has become part of the standard care in patients treated with EGFR targeting therapy. Testing for KRAS mutations is not standardized, there is a multitude of methods, some of which are commercially available CE marked techniques. Most frequently used assays are developed in this review. It is very difficult today to tell which test is the most reliable. Moreover tumour samples are very heterogeneous (fixation, biopsy, surgical specimen, neoadjuvant treatment) and one “best” method could depend upon the type of sample. A STIC program is on going in France (MOKAECM) to initiate a quality assurance (QA)-program for KRAS testing. All INCa labelled laboratories that develop somatic oncology genetic tests participate to this program. Methods will be tested on cell line DNAs at first, then DNAs from paraffin embedded tumours will be shared and typed by the various laboratories. Finally, an economical evaluation will be done to compare techniques at all levels. This is of importance since KRAS testing needs to be done in a wide numbers of laboratories with similar value. KRAS testing is the first predictive genetic test in a frequent solid tumour, the establishment of a QA-program can serve as a future example for the introduction of other markers based on tumour genetic alterations.