Genetic variation of acquired structural chromosomal aberrations

Publication date: Available online 19 May 2018 Source:Mutation Research/Genetic Toxicology and Environmental Mutagenesis Author(s): Pavel Vodicka, Ludovit Musak, Ludmila Vodickova, Sona Vodenkova, Calogerina Catalano, Michal Kroupa, Alessio Naccarati, Zdena Polivkova, Veronika Vymetalkova, Asta Försti, Kari Hemminki 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 o...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research