Molecular analysis of Kras and Nras mutations in a series of 720 patients for guiding the treatment of metastatic colorectal cancer in Turkey.

e13115 Background: Mutations in Kras and Nras genes in primary colorectal tumors are the reasons for nonresponse to anti-epidermal growth factor receptor (EGFR) antibodies in patients with metastatic colorectal cancer (mCRC). Results of the molecular analysis guides the treatment decision-making in mCRC. The aim of this study was to evaluate the Kras and Nras mutation data from 720 patients with mCRC between 01 January 2015 and 31 January 2016 using minisequencing method. Methods: We performed a two round nested PCR for the amplification of Exons 1, 2, 3 of Kras and Nras genes harbouring codons 12, 13, 59, 61, 117, and 146 followed by a multiplex minisequencing reaction for the detection of potential mutations. Results: A total of 720 patients were analysed for the mutations in codons 12, 13, 59, 61, 117, and 146 of Kras and Nras genes. Results were obtained from 718 out of 720 (99,72%) patients and no results were obtained from 2 (0,28%) of the cases. 400/718 (55,71%) patients were wild-type for Kras mutations while 318 of them carried a Kras mutation (44,29%). 8 of 318 (2,52%) patients carried two mutations which made totally 326 Kras mutations. Kras mutation rates were 192/326 (58,90%), 98/326 (30,06%), 3/326 (0,92%), 8/326 (2,45%), 3/326 (0,92%), 22/326 (6,75%) in codons 12, 13, 59, 61, 117, 146 respectively. Additional Nras mutation testing was performed for 400 patients which were found to be wild-type for Kras mutations. 31/400 (7,75%) patients were found to carry Nras mutations while 369 (92,25%) of them were wild-type for Nras mutations. 1 of 31 (3,23%) patients carried two mutations which made totally 32 Nras mutations. Mutation distribution was 10/32 (31,25%), 4/32 (12,50%), 4/32 (12,50%), 11/32 (34,38%), 2/32 (6,25%), 1/32 (3,13%) in codons 12, 13, 59, 61, 117, 146 respectively. Conclusions: High rate (349/718, 48,61%) of mutation finding in Kras and Nras testing makes mutation profiling in Kras and Nras genes an effective approach to select patients who are more likely to respond to anti-EGFR immunotherapy or rule out this treatment for those who are not likely to respond, and predict patient outcomes using minisequencing reaction which is a highly sensitive and cost effective method.