26 March 2009

Epigenetics and cancer: a dangerous gene named BORIS

Epigenetic changes may initiate the development of cancer in more than half of the patientsDmitry Safin, Compulenta

Oncologists have long established that increasing the level of DNA methylation (the essence of the methylation process is modification – the addition of a methyl group to the nitrogenous base cytosine without changing the nucleotide sequence; such modifications are commonly called epigenetic) of certain genes can contribute to the development of cancer.

A group of researchers from Johns Hopkins University (USA), who studied demethylation (the reverse process of the above), found that it is also capable of causing the activation of oncogenes.

The scientists' conclusions are based on the results of a simple and convincing experiment: they treated two different lines of oral tissue cells with the drug 5-azacitidine, which is based on demethylation, and identified all the genes activated under the influence of the drug. The resulting list was then compared with a list of genes "turned on" in 49 samples of head and neck tumor cells and 19 samples of healthy tissue. The comparison revealed 106 genes associated with head and neck cancer that were activated by demethylation. "Some of them regulate cell growth, others affect the digestibility of sugars, and some have long been associated with the development of cancer," notes Joseph Califano, one of the authors of the study.

Further analysis of the collected data allowed scientists to find a connection between all 106 genes: the level of their methylation is determined by another gene, called BORIS (some information about it can be obtained from an article published by the British Journal of Cancer). According to the information available to researchers, about sixty percent of cancer patients show an increased level of expression of the BORIS gene. (An illustration from an article published in BJC – breast cell lines showing different levels of expression of the BORIS gene. Staining was performed using hematoxylin and antibodies.)

It should be noted that the work of American specialists can radically change the attitude of oncologists to existing drugs of demethylating action: it is obvious that in some cases such drugs can cause the development of new tumors. "Of course, it is too early to draw any conclusions, but we assume that patients will have to undergo additional examinations before starting demethylation treatment," Mr. Califano summarizes.

The full version of the scientists' report is published in the journal PLoS One.

Prepared based on the materials of PhysOrg.

Portal "Eternal youth" www.vechnayamolodost.ru26.03.2009

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