A Multiplex SNaPshot Assay as a Rapid Method for Detecting KRASand BRAFMutations in Advanced Colorectal Cancers

Autor: Magnin, Sandrine, Viel, Erika, Baraquin, Alice, Valmary-Degano, Severine, Kantelip, Bernadette, Pretet, Jean-Luc, Mougin, Christiane, Bigand, Marthe, Girardo, Benoît, Borg, Christophe, Ferrand, Christophe
Zdroj: The Journal of Molecular Diagnostics; September 2011, Vol. 13 Issue: 5 p485-492, 8p
Abstrakt: The analysis of KRASmutations has become a prerequisite for anti-epidermal growth factor receptor therapy in patients with metastatic colorectal cancers. KRASmutations are associated with resistance to treatment by monoclonal antibodies such as cetuximab and panitumumab and thus are correlated with a shorter progression-free survival. BRAFmutations also may play a role in treatment decisions. The widespread use of these targeted therapies has generated the need to develop cost-effective methods for routine KRASand BRAFanalysis. The aim of this study was to compare a multiplex SNaPshot assay with DNA sequencing and high-resolution melting analysis for identifying KRAScodons 12 and 13 and BRAFcodon 600 mutations. Thus 110 routinely formalin-fixed and paraffin-embedded tissue blocks were tested by each method. The SNaPshot analysis detected KRASand BRAFcodon 600 mutations in, respectively, 34.5% (n= 38) and 10% (n= 11) of these tissue blocks. These results were confirmed by direct DNA sequencing and by high-resolution melting analysis. The costs and time constraints of each detection method were compared at the same time. In conclusion, our newly designed multiplex SNaPshot assay is a fast, inexpensive, sensitive, and robust technique for molecular diagnostic practices and patient selection.
Databáze: Supplemental Index