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. 2014;36(6):9730.
doi: 10.1007/s11357-014-9730-4. Epub 2014 Nov 16.

Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging

Idoia Martín-Guerrero  1 , Elena de Prado, Elixabet Lopez-Lopez, Maite Ardanaz, Juan Carlos Vitoria, Luis A Parada, Cristina García-Orad, Africa García-Orad
Affiliations

Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging

Idoia Martín-Guerrero et al. Age (Dordr). 2014.

Abstract

Chromosome translocations are especially frequent in human lymphomas and leukemias but are insufficient to drive carcinogenesis. Indeed, several of the so-called tumor specific translocations have been detected in peripheral blood of healthy individuals, finding a higher frequency of some of them with aging. The inappropriate repair of DNA double strand breaks by the nonhomologous end joining (NHEJ) pathway is one of the reasons for a translocation to occur. Moreover, fidelity of this pathway has been shown to decline with age. Although the mechanism underlying this inefficacy is unknown, other repair pathways are inactivated by methylation with aging. In this study, we analyzed the implication of NHEJ genes methylation in the increase of translocations with the age. To this aim, we determined the relationship between translocations and aging in 565 Spanish healthy individuals and correlated these data with the methylation status of 11 NHEJ genes. We found higher frequency of BCL2-JH and BCR-ABL (major) translocations with aging. In addition, we detected that two NHEJ genes (LIG4 and XRCC6) presented age-dependent promoter methylation changes. However, we did not observe a correlation between the increase of translocations and methylation, indicating that other molecular mechanisms are involved in the loss of NHEJ fidelity with aging.

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Figures

Fig. 1
Fig. 1
Prevalence of translocation positivity according to the age of individuals. For BCL-JH, a total of 545 individuals were analyzed (298 < 40 vs 247 > 40 years old). For the BCR-ABL, MLL-AF4 and TEL-AML1 chromosome translocations, 171 individuals were studied (83 < 40 vs 88 > 40 years old). Asterisk represents statistically significant results
Fig. 2
Fig. 2
Methylation-specific PCR results. The percentage of methylation in 9 CpG islands was compared in young people ≤20 years old vs adults >40 years old. Asterisk represents statistically significant results
See this image and copyright information in PMC

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