DNA hypomethylation as Achilles’ heel of tumorigenesis: A working hypothesis

There are at least two findings that show DNA hypomethylation plays a key role in carcinogenesis. The first major evidence is that DNA hypomethylation induces target chromosomal and genomic instability with cancer manifestations. The second reason that cancer progression is associated with deepening...

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Bibliographic Details
Published in:Cell biology international 2009-08, Vol.33 (8), p.904-910
Main Author: Shvachko, L.P.
Format: Article
Language:English
Subjects:
5-Azacytidine
Azacitidine - pharmacology
DNA hypomethylation
DNA Methylation
Epigenesis, Genetic
Heterochromatin - genetics
Interphase
Karyotyping
Latent polytene heterochromatinization
Lymphocytes - drug effects
Lymphocytes - metabolism
Metaphase
Neoplasms - genetics
Pericentromeric heterochromatin
Ploidies
Somatic cancer cell biology
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Summary:There are at least two findings that show DNA hypomethylation plays a key role in carcinogenesis. The first major evidence is that DNA hypomethylation induces target chromosomal and genomic instability with cancer manifestations. The second reason that cancer progression is associated with deepening DNA hypomethylation. Nevertheless, the evolution of this crucial epigenomic alteration in the somatic cellular malignant transformation remains unclear. From some of the experimental data to be present, a key role of DNA hypomethylation in early development of epigenetic somatic cancer biology is proposed. We have observed the significant increasing of genome ploidy at the level of peripheral blood lymphocytes taken from the patients with different solid carcinomas. Similarly, 5-azacytidine demethylating DNA treatment of cultured healthy lymphocytes induces increased nuclear DNA content. We argue that somatic lymphocyte ploidy induced by genomic DNA hypomethylation during carcinogenesis is related to global demethylation and decondensation of mitotic constitutive pericentromeric heterochromatin. This results in disturbances of pericentromeric heterochromatin that are expressed in nuclear heterochromatinization on the basis of extrachromosomal chromomerization. On the basis of literature searches and experimental findings, it is proposed that DNA hypomethylation plays the role of an initiator in epigenetic somatic cancer biology.
ISSN:1065-6995
1095-8355
DOI:10.1016/j.cellbi.2009.02.018