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      https://www.ias.ac.in/article/fulltext/jbsc/040/05/0873-0883

    • Keywords

       

      K-RAS; lung cancer; NF-Y binding; regulatory SNPs (rSNP)

    • Abstract

       

      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.

    • Author Affiliations

       

      Elena V Antontseva1 Marina Yu Matveeva1 Natalia P Bondar1 Elena V Kashina1 Elena Yu Leberfarb1 Leonid O Bryzgalov1 Polina A Gervas2 Anastasia A Ponomareva2 3 Nadezhda V Cherdyntseva2 Yury L Orlov1 4 Tatiana I Merkulova1 4

      1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Lavrentieva avenue 10, Novosibirsk 630090, Russian Federation
      2. Tomsk Cancer Research Institute, Kooperativny Lane 5, Tomsk 634050, Russian Federation
      3. Tomsk Polytechnical University, Lenina Avenue, 32, Tomsk 634050, Russian Federation
      4. Novosibirsk State University, Pirogova Street 2, Novosibirsk 630090, Russian Federation
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