Prevalence and Heterogeneity of KRAS, BRAF, and PIK3CA Mutations in Primary Colorectal Adenocarcinomas and Their Corresponding Metastases

摘要: Purpose: Epidermal growth factor receptor (EGFR) antibody therapy is established in patients with wild-type KRAS colorectal carcinoma; however, up to 50% of these do not respond this therapy. To identify the possible causes failure, we searched for mutations different EGFR-dependent signaling proteins and analyzed their distribution patterns primary tumors corresponding metastases. Experimental Design: Tumor tissues, macrodissected from tumor centers, invasion fronts ( n = 100), lymph nodes 55), distant metastases 20), respectively, were subjected DNA extraction mutation analysis KRAS, BRAF , PIK3CA . Results: Activating detected 41% ), 7% 21% ) tumors. By comparing centers fronts, intratumoral heterogeneity was observed 8%, 1%, 5% tumors, respectively. Heterogeneity between node found 31% 4% 13% cases. present two (10%) one patient (5%), but Discordant results could markedly be reduced by testing additional samples. Conclusions: Failure EGFR cancer may result activating or false-negative sequencing caused heterogeneity. Due particularly high rates metastases, latter are least suitable diagnostic analysis. Clin Cancer Res; 16(3); 790–9