Jean-Yves Douillard, M online .D., Ph.D., Kelly S. Oliner, Ph.D., Salvatore Siena, M.D., Josep Tabernero, M.D., Ronald Burkes, M.D., Mario Barugel, M.D., Yves Humblet, M.D., Ph.D., Gyorgy Bodoky, M.D., Ph.D., David Cunningham, M.D., Jacek Jassem, M.D., Ph.D., Fernando Rivera, M.D., Ph.D.D., Ph.D., Paul Ruff, M.D.D.D., Jean Luc Canon, M.D., Tag Rother, M.D., Richard Williams, M.B., B.S., Ph.D., Alan Rong, Ph.D., Jeffrey Wiezorek, M.D., Roger Sidhu, M.D., and Scott D. Patterson, Ph.D.1-4 Specifically, patients with KRAS mutations in exon 2 do not have a reply to anti-EGFR therapy and may have inferior outcomes if this therapy is combined with an oxaliplatin-containing chemotherapy routine.
Whole-cell patch-clamp procedures were used to measure expressed currents and their response to pH and pharmacologic brokers. Detailed methods for the molecular biologic and electrophysiological studies are provided in the Supplementary Appendix. Results Whole-Exome Sequencing The average depth of sequence coverage of the whole-exome sequencing data was 78. We eliminated variants that acquired an allele frequency of more than 1 percent in established databases, including dbSNP, the 1000 Genomes Project, and the National Center, Lung, and Bloodstream Institute Exome Variant Server.