Genetic variation of acquired structural chromosomal aberrations

Research output: Contribution to journalArticle


Human malignancies are often hallmarked with genomic instability, which itself is also considered a causative event in malignant transformation. Genomic instability may manifest itself as genetic changes in the nucleotide sequence of DNA, or as structural or numerical changes of chromosomes. Unrepaired or insufficiently repaired DNA double-strand breaks, as well as telomere shortening, are important contributors in the formation of structural chromosomal aberrations (CAs). In the present review, we discuss potential mechanisms behind the formation of CAs and their relation to cancer. Based on our own studies, we also illustrate how inherited genetic variation may modify the frequency and types of CAs occurring in humans. Recently, we published a series of studies on variations in genes relevant to maintaining genomic integrity, such as those encoding xenobiotic-metabolising enzymes, DNA repair, the tumour suppressor TP53, the spindle assembly checkpoint, and cyclin D1 (CCND1). While individually genetic variation in these genes exerted small modulating effects, in interactions they were associated with CA frequencies in peripheral blood lymphocytes of healthy volunteers. Moreover, we observed opposite associations between the CCND1 splice site polymorphism rs9344 G870A and the frequency of CAs compared to their association with translocation t(11,14). We discuss the functional consequences of the CCND1 gene in interplay with DNA damage response and DNA repair during malignant transformation. Our review summarizes existing evidence that gene variations in relevant cellular pathways modulate the frequency of CAs, predominantly in a complex interaction. More functional/mechanistic studies elucidating these observations are required. Several questions emerge, such as the role of CAs in malignancies with respect to a particular phenotype and heterogeneity, the formation of CAs during the process of malignant transformation, and the formation of CAs in individual types of lymphocytes in relation to the immune response.


  • Pavel Vodicka
  • Ludovit Musak
  • Ludmila Vodickova
  • Sona Vodenkova
  • Calogerina Catalano
  • Michal Kroupa
  • Alessio Naccarati
  • Zdena Polivkova
  • Veronika Vymetalkova
  • Asta Försti
  • Kari Hemminki
External organisations
  • Institute of Experimental Medicine, Czech Academy of Science
  • Charles University in Prague
  • German Cancer Research Centre
  • Center for Primary Health Care Research
  • Comenius University
  • Italian Institute for Genomic Medicine (IIGM)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics


  • Chromosomal aberrations, Cyclin D1, DNA repair, Genetics, Mitotic checkpoints, Xenobiotic metabolizing enzymes
Original languageEnglish
Pages (from-to)13-21
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Early online date2018 May 19
Publication statusPublished - 2018
Publication categoryResearch