Tatiana I Merkulova
Articles written in Journal of Biosciences
Volume 40 Issue 5 December 2015 pp 873-883 Articles
Elena V Antontseva Marina Yu Matveeva Natalia P Bondar Elena V Kashina Elena Yu Leberfarb Leonid O Bryzgalov Polina A Gervas Anastasia A Ponomareva Nadezhda V Cherdyntseva Yury L Orlov Tatiana I Merkulova
There are two regulatory single nucleotide polymorphisms (rSNPs) at the beginning of the second intron of the mouse 𝐾-𝑟𝑎𝑠 gene that are strongly associated with lung cancer susceptibility. We performed functional analysis of three SNPs (rs12228277: T>A, rs12226937: G>A, and rs61761074: T>G) located in the same region of human 𝐾𝑅𝐴𝑆. We found that rs12228277 and rs61761074 result in differential binding patterns of lung nuclear proteins to oligonucleotide probes corresponding two alternative alleles; in both cases, the transcription factor NF-Y is involved. G>A substitution (rs12226937) had no effect on the binding of lung nuclear proteins. However, all the nucleotide substitutions under study showed functional effects in a luciferase reporter assay. Among them, rs61761074 demonstrated a significant correlation with allele frequency in non-small-cell lung cancer (NSCLC). Taken together, the results of our study suggest that a T>G substitution at nucleotide position 615 in the second intron of the KRAS gene (rs61761074) may represent a promising genetic marker of NSCLC.