Clinical Utility Of Expanded Screening Of The Kras And Nras Genes For Metastatic Colorectal Cancer: Evaluation Of The Crc Rascan Tumor Test As A Companion Diagnostic To Determine Efficacy Of Anti-Egfr Therapies.

e12554 Background: RAS family genes affect signal transduction downstream of EGFR and play a critical role in determining response to EGFR-targeted therapies. Primary resistance to EGFR-specific Tyrosine Kinase Inhibitors (including cetuximab and panitumumab) in colon cancer is often due to the presence of RAS mutations. KRAS and NRAS mutations are found in ~25% of human tumors and lead to constitutive activation of Ras proteins. About 35-45% of colorectal tumors carry KRAS Exon 2 (codon 12 and 13) mutations which constitutively activate signaling downstream of EGFR. Presence of KRAS Exon 2 mutation status therefore predicts response to anti-EGFR therapy. However, ~10% of patient tumors that do not have a mutation in KRAS exon 2, have been found recently to harbor mutations in KRAS exons 3 or 4 or in NRAS exons 2, 3, or 4. Methods: The Transgenomic CRC RAScan test was developed to offer expanded screening of the KRAS and NRAS genes across exons 2, 3 and 4 respectively to better guide management decision m...