[Searching for essential genes in cancer genomes]

Biomed Khim. 2018 Aug;64(4):303-314. doi: 10.18097/PBMC20186404303.
[Article in Russian]

Abstract

The concept of essential genes, whose loss of functionality leads to cell death, is one of the fundamental concepts of genetics and is important for fundamental and applied research. This field is particularly promising in relation to oncology, since the search for genetic vulnerabilities of cancer cells allows us to identify new potential targets for antitumor therapy. The modern biotechnology capacities allow carrying out large-scale projects for sequencing somatic mutations in tumors, as well as directly interfering the genetic apparatus of cancer cells. They provided accumulation of a considerable body of knowledge about genetic variants and corresponding phenotypic manifestations in tumors. In the near future this knowledge will find application in clinical practice. This review describes the main experimental and computational approaches to the search for essential genes, concentrating on the application of these methods in the field of molecular oncology.

Poniatie kriticheski vazhnykh genov, ch'ia utrata funktsii privodit k gibeli kletki, iavliaetsia odnoĭ iz osnovopolagaiushchikh kontseptsiĭ genetiki i imeet vazhnoe znachenie dlia fundamental'nykh i prikladnykh issledovaniĭ. Osobenno perspektivno izuchenie dannoĭ oblasti primenitel'no k onkologii, poskol'ku poisk geneticheskikh uiazvimosteĭ rakovykh kletok pozvoliaet vyiavit' novye potentsial'nye misheni dlia protivoopukholevoĭ terapii. Sovremennye vozmozhnosti biotekhnologiĭ pozvoliaiut provodit' krupnomasshtabnye proekty po sekvenirovaniiu somaticheskikh mutatsiĭ v opukholiakh, a takzhe napriamuiu vmeshivat'sia v rabotu geneticheskogo apparata rakovykh kletok. Blagodaria étomu nakoplen znachitel'nyĭ massiv znaniĭ o vstrechaiushchikhsia geneticheskikh variantakh i ikh fenotipicheskikh proiavleniiakh. Ne vyzyvaet somneniia, chto v nedalekom budushchem éti znaniia naĭdut primenenie v klinicheskoĭ praktike. V nastoiashchem obzore opisany osnovnye éksperimental'nye i vychislitel'nye podkhody k poisku kriticheski vazhnykh genov, kontsentriruias' na primenenii étikh metodov v oblasti molekuliarnoĭ onkologii.

Keywords: CRISPR; RNAi; cancer genome; essential genes; synthetic lethals.

Publication types

  • Review

MeSH terms

  • CRISPR-Associated Protein 9 / genetics
  • CRISPR-Cas Systems / genetics
  • Evolution, Molecular
  • Genes, Essential*
  • Genome, Human*
  • Humans
  • Neoplasms / genetics*
  • RNA Interference

Substances

  • CRISPR-Associated Protein 9