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Cyclin D1 splice site variant triggers chromosomal aberrations in healthy humans

Leukemia volume 28, pages 721–722 (2014)Cite this article

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Chromosomal aberrations (CAs) were suggested to be the cause of cancer by Boveri already a 100 years ago, but the detection of the Philadelphia chromosome about 50 years later provided the first direct evidence on the relationship (reviewed by Mitelman1). CAs include recurrent aberrations, including specific translocations, deletions and amplifications of chromosomal regions or whole chromosomes. The detection of recurrent CAs was greatly facilitated when fluorescence in situ hybridization techniques were developed for interphase chromosomes. Non-specific CAs include missing, fragmented or fused chromosomal segments, divided into chromosome-type aberrations (CSAs) and chromatid-type aberrations (CTAs).2 These have been conventionally analyzed by microscopic scoring of metaphase nuclei from cultured lymphocytes. Modern sequencing techniques have revealed numerous gene fusions and rearrangements, in the extreme, chromothripsis, a catastrophic parsing of illegitimate chromosomal segments together.3

Non-specific CAs may arise as a result of direct DNA damage by, for example, ionizing radiation or replication on a damaged DNA template; the former lesions would be detected as CSAs, whereas the latter may be CSAs or CTAs.2 Non-specific CAs remain in lymphocytes for their lifetime.2 They have been used in monitoring of radiation exposure and exposure to genotoxic compounds and, together with sister chromatid exchanges and micronuclei, CAs have offered the only available method for human biomonitoring for genotoxic exposures. There are convincing data on the association of CA frequency with subsequent risk of many cancers.4 Furthermore, patients with many types of cancer show increased frequencies of CAs at diagnosis.5 CAs were assumed to be somatic events but our recent study on multiple myeloma showed that the recurrent t(11;14) (q13;q32) translocation was strongly associated with the cyclin D1 (CCND1) G870A genotype at a splice site.6 However, no effect was found for any other translocations or other CAs in myeloma. Here, we wanted to test the possible dependence of non-specific CAs on the CCND1 genotype by assaying for the G870A genotype in a large cohort of persons for whom CAs were measured. This polymorphism has been implicated as a risk factor for a number of cancers.7, 8

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Authors and Affiliations

  1. Department of Molecular Genetic Epidemiology, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany

    K Hemminki & A Försti

  2. Center for Primary Health Care Research, Lund University, Malmö, Sweden

    K Hemminki & A Försti

  3. Clinic of Occupational Medicine and Toxicology, Jessenius Faculty of Medicine, Comenius University and University Hospital Martin, Martin, Slovakia

    L Musak & O Osina

  4. Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    V Vymetalkova, L Vodickova & P Vodicka

  5. Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic

    V Vymetalkova, Z Smerhovsky, L Vodickova & P Vodicka

  6. 2nd Faculty of Medicine, Charles University, Prague, Czech Republic

    Z Smerhovsky

  7. Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia

    E Halasova

  8. Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia

    L Letkova

  9. Department of Public Health, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.

    J Buchancova

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  1. K Hemminki
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Correspondence to K Hemminki.

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Hemminki, K., Musak, L., Vymetalkova, V. et al. Cyclin D1 splice site variant triggers chromosomal aberrations in healthy humans. Leukemia 28, 721–722 (2014). https://doi.org/10.1038/leu.2013.353

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