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Journal of Biosciences

, Volume 40, Issue 5, pp 873–883 | Cite as

Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS gene

  • Elena V Antontseva
  • Marina Yu MatveevaEmail author
  • 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
Article

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.

Keywords

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

Notes

Acknowledgements

The research has been carried out with support of the grant from Russian Academy of Science Program Fundamental Science for Medicine #23, and Federal Targeted Programmer for Research and Development in Priority Areas of Development of the Russian Scientific and Technological Complex for 2014-2020, Development of Molecular Signatures for Early Detection of Lung Cancer (No. 14.575.21.0064 from 05.08.2014) and State Budget Project N VI.58.1.2.

Supplementary material

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ESM 1 (PDF 970 kb)

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Copyright information

© Indian Academy of Sciences 2015

Authors and Affiliations

  • Elena V Antontseva
    • 1
  • Marina Yu Matveeva
    • 1
    Email author
  • Natalia P Bondar
    • 1
  • Elena V Kashina
    • 1
  • Elena Yu Leberfarb
    • 1
  • Leonid O Bryzgalov
    • 1
  • Polina A Gervas
    • 3
  • Anastasia A Ponomareva
    • 3
    • 4
  • Nadezhda V Cherdyntseva
    • 3
  • Yury L Orlov
    • 1
    • 2
  • Tatiana I Merkulova
    • 1
    • 2
  1. 1.Institute of Cytology and Genetics, Siberian BranchRussian Academy of SciencesNovosibirskRussian Federation
  2. 2.Novosibirsk State UniversityNovosibirskRussian Federation
  3. 3.Tomsk Cancer Research InstituteTomskRussian Federation
  4. 4.Tomsk Polytechnical UniversityTomskRussian Federation

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