Frequency of somatic mutations in the KRAS gene in patients of the South Russia diagnosed with colorectal cancer.

Abstract

e15081 Background: Colorectal cancer (CRC) is a common pathology in the world; the annual incidence rate reaches 1 million cases, and the annual mortality rate exceeds 500,000. The target therapy of EGFR with monoclonal drugs improves the survival of patients with this pathology. However, the effectiveness of therapy depends on the presence of mutations in genes involved in the EGFR signaling cascade, in particular KRAS. The purpose of this study was to determine the frequency of somatic mutations in the KRAS gene in tumor samples of patients from the South Russia diagnosed with colorectal cancer, as well as to analyze the effect of point mutations G12A, G12C, G12D, G12R, G12S, G12V and G13D on tumor metastasis. Methods: 744 patients diagnosed with colorectal adenocarcinoma were examined for mutations in 12th and 13th codons of KRAS. Somatic mutations in the KRAS gene were detected with reagent kit Biolink (Russia) using FFPE DNA samples of tumor tissues. Statistical analysis was performed using the method of binary logistic multiple regression and χ2-test. Results: Mutations in the KRAS gene were found in 32% of patients in the pooled sample; the most common mutation was the replacement of G12D in the KRAS gene (36%). Less common detectable mutations in the KRAS gene were G13D (18%), G12V (16%), G12A (10%), G12C (8%), G12S (10%), G12R (2%). Metastatic CRC was found in 86% of carriers of the wild-type allele and in 88% of carriers of the mutant allele. The presence of a G12V substitution almost 6 times increased the risk of metastasis in patients with CRC (OR = 5.89; 95% CI: 0.8-43.45; p = 0.049). Conclusions: Mutations in the KRAS gene were found in 32% of patients with CRC in the South of Russia. A significant association of G12V replacement with a high risk of metastasis was established. Further study of somatic mutations in the KRAS gene will allow to choose the most effective therapeutic strategies in the presence of one or another of the studied mutations.

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…The frequency of KRAS mutations (exon 2 and exon 3) in our cohort reached 61.88%. This was much higher than what was reported in the Asia-Pacific (37-52%) and Western populations (32-49%) [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Nevertheless, our data is in line with a previous study in Indonesia, showing that KRAS mutation was found in 71.8% of serrated adenocarcinoma (SA), which is intriguingly higher than the generally reported incidence of 40% [39][40][41].…”

“…Colorectal cancer (CRC) is the third most prevalent cancer worldwide and as well as one of the most deadly. Approximately in Indonesia, over 35,000 patients are diagnosed with CRC each year [1].…”