Genetic variation in the major mitotic checkpoint genes associated with chromosomal aberrations in healthy humans

Research output: Contribution to journalArticle


Non-specific chromosomal aberrations (CAs) are microscopically detected in about 1% of lymphocytes drawn from healthy persons. Causes of CAs in general population are not known but they may be related to risk of cancer. In view of the importance of the mitotic checkpoint machinery on maintaining chromosomal integrity we selected 9 variants in main checkpoint related genes (BUB1B, BUB3, MAD2L1, CENPF, ESPL1/separase, NEK2, PTTG1/securin, ZWILCH and ZWINT) for a genotyping study on samples from healthy individuals (N = 330 to 729) whose lymphocytes had an increased number of CAs compared to persons with a low number of CAs. Genetic variation in individual genes played a minor importance, consistent with the high conservation and selection pressure of the checkpoint system. However, gene pairs were significantly associated with CAs: PTTG1-ZWILCH and PTTG1-ZWINT. MAD2L1 and PTTG1 were the most common partners in any of the two-way interactions. The results suggest that interactions at the level of cohesin (PTTG1) and kinetochore function (ZWINT, ZWILCH and MAD2L1) contribute to the frequency of CAs, suggesting that gene variants at different checkpoint functions appeared to be required for the formation of CAs.


  • Asta Försti
  • Christoph Frank
  • Bozena Smolkova
  • Alena Kazimirova
  • Magdalena Barancokova
  • Veronika Vymetalkova
  • Michal Kroupa
  • Alessio Naccarati
  • Ludmila Vodickova
  • Janka Buchancova
  • Maria Dusinska
  • Ludovit Musak
  • Pavel Vodicka
  • Kari Hemminki
External organisations
  • German Cancer Research Centre
  • Slovak Academy of Sciences
  • Slovak Medical University
  • Charles University in Prague
  • Human Genetics Foundation (HuGeF)
  • Comenius University
  • Norwegian Institute for Air Research
  • University Hospital Martin
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics


  • Chromosomal integrity, Cytogenetics, DNA double-stranded break, Spindle checkpoint
Original languageEnglish
Pages (from-to)442-446
Number of pages5
JournalCancer Letters
Issue number2
Publication statusPublished - 2016 Oct 1
Publication categoryResearch