BRCA Mutations—The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers

Anna P. Loboda, Leonid S. Adonin, Svetlana D. Zvereva, Dmitri Y. Guschin, Tatyana V. Korneenko, Alexandra V. Telegina, Olga K. Kondratieva, Sofia E. Frolova, Nikolay B. Pestov, Nick A. Barlev

Research output: Contribution to journalReview articlepeer-review

3 Citations (Scopus)

Abstract

Two related tumor suppressor genes, BRCA1 and BRCA2, attract a lot of attention from both fundamental and clinical points of view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset of breast and ovarian cancers. However, the molecular mechanisms that drive extensive mutagenesis in these genes are not known. In this review, we hypothesize that one of the potential mechanisms behind this phenomenon can be mediated by Alu mobile genomic elements. Linking mutations in the BRCA1 and BRCA2 genes to the general mechanisms of genome stability and DNA repair is critical to ensure the rationalized choice of anti-cancer therapy. Accordingly, we review the literature available on the mechanisms of DNA damage repair where these proteins are involved, and how the inactivating mutations in these genes (BRCAness) can be exploited in anti-cancer therapy. We also discuss a hypothesis explaining why breast and ovarian epithelial tissues are preferentially susceptible to mutations in BRCA genes. Finally, we discuss prospective novel therapeutic approaches for treating BRCAness cancers.

Original languageEnglish
Article number4982
JournalInternational journal of molecular sciences
Volume24
Issue number5
DOIs
Publication statusPublished - Mar 2023
Externally publishedYes

Keywords

  • Alu repeats
  • breast cancer
  • ovarian cancer
  • PARP inhibitors
  • protein-protein interactions

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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