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Polymorphisms in the DNA ligase IV gene might influence the risk of acute lymphoblastic leukemia in children

Leukemia volume 21, pages 2226–2227 (2007)Cite this article

Chromosomal abnormalities are a hallmark of both pediatric and adult acute lymphoblastic leukemia (ALL) (reviewed in Armstrong and Look1) and there is substantial evidence that defects in the repair of DNA damage can play an important role in the development of lymphoid malignancies. Two major pathways for the repair of DNA double-strand breaks (DSB), considered as the most lethal form of DNA damage for eukaryotic cells, are known.2 While during late S- and G2-phase DSB can be repaired by homologous recombination with the sister chromatid, non-homologous end joining (NHEJ) is the predominant if not exclusive pathway during G0-, G1- and early S-phase. NHEJ, however, is typically imprecise due to the end processing of DNA ends before ligation. One of the central components of NHEJ is the DNA ligase IV (LIGIV) (reviewed in Lieber et al.3).

It has been shown that mutations in the LIGIV gene could lead to the rare LIGIV syndrome, which clinically resembles the Nijmegen breakage syndrome (NBS). Since only few patients with LIGIV deficiency have been described, it is still unknown whether this syndrome, like NBS and ataxia teleangiectatica, is also associated with an increased cancer risk. However, the first patient with a known defect in NHEJ who was homozygous for a missense mutation in LIGIV developed an ALL at the age of 14 years (reviewed in O'Driscoll et al.4 and Girard et al.5). From the evidence presented above, LIGIV involved in NHEJ is a plausible candidate gene for a cancer predisposition syndrome. Thus, we aimed to test whether mutations in the gene encoding LIGIV might increase the risk of developing ALL during childhood.

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Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany

    J Andreae & K Seeger

  2. Institute of Human Genetics, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany

    R Varon & K Sperling

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  1. J Andreae
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  2. R Varon
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  4. K Seeger
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Correspondence to K Seeger.

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Andreae, J., Varon, R., Sperling, K. et al. Polymorphisms in the DNA ligase IV gene might influence the risk of acute lymphoblastic leukemia in children. Leukemia 21, 2226–2227 (2007). https://doi.org/10.1038/sj.leu.2404783

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