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Epigenetic activation of ribosomal cistrons of the chromatids of the 15th acrocentric chromosome in lung cancer
After the completion of the Human genome project, the strategic direction of modern genetics shifted towards functional genomics, which also studies noncoding regions of DNA, located in heterochromatin. Most functions of heterochromatin are yet to be determined. Shortarm telomeres of each human acrocentric chromosome (13, 14, 15, 21, and 22) have satellite strands, called nucleolar organizer regions (NORs), which consist of heterochromatin. Human NORs contain from 250 to 670 gene replicas of ribosomal RNA (rRNA) and only 50 % of these replicas are transcribed. The satellite strands of chromatids in some acrocentric chromosomes are united, forming «satellite associations» (SAs), which are always transcriptionally active. The phenomenon of SA lies in the fact that it is a highly specific indicator of the structure and function of the nucleolus in the preceding interphase. rDNA in human genome may be subject to changes due to cancer. In this study, we determined the epigenetic variability of ribosomal cistrons in lung cancer (LC). It was found that the frequency of chromatid SAs per cell was reliably increased (p < 0.05) in patients with LC (1.76 ± 0.08) as compared with the similar index for clinically healthy persons, aged 22–45 (control group) (1.35 ± 0.03). The associative activity of chromatids of the 15th chromosome was decreased in the control group (p < 0.01) as compared with the activity of chromatids of other chromosomes. Contrary to the control group, in patients with LC the chromatids of the 15th chromosome manifested higher involvement in the associations (p < 0.05) than the chromatids of other acrocentric chromosomes, which corresponded to the order: 15> 13 = 14> 21> 22. A similar phenomenon was observed for the associations of chromatids of homologous chromosomes (15 : 15) in patients with LC, which reliably exceeded the index for this type of SA in healthy middleaged people (p < 0.001). Our results demonstrated that the differential activity of satellite strands of the chromatids of the 15th chromosome in patients with LC is subject to epigenetic variability which highlights the relevance of studying SAs for diagnostics and elaboration of treatment strategy. The studies on epigenetic variability of ribosomal cistrons of acrocentric chromatids under pathology is a new direction in medicine, aimed at diagnostics of diseases and determining a new treatment strategy in future.
Key words: chromatid associations, heterochromatinization, lung cancer, NOR, satellite strands
E-mail: lezhavat yahoo.com
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