15 November 2022

Does the X chromosome protect against cancer?

It is known that cancer cells grow and multiply uncontrollably due to the accumulation of genetic abnormalities. A new study by the Dana-Farber Cancer Institute found another difference between cancer and normal cells: one of the two X chromosomes, usually inactivated only in female somatic cells, can be suppressed in various types of cancer in men.

Using publicly available datasets consisting of thousands of DNA samples from cancer patients around the world, a group of researchers led by oncologist geneticist Srinivas Viswanathan found high expression of the XIST gene responsible for suppressing gene expression in the X chromosome in about 4% of analyzed cancer samples in men.

Normally, XIST is active in the early stages of development in both sexes and in older women. It has previously been shown that some female cancer cells may lose the ability to turn off one of the X chromosomes, which leads to increased expression of X-linked genes. In men, the ability to inactivate X has not been studied specifically.

Of the 4% of the abnormalities detected in men, 74% were tumors of the reproductive system, which, as was already known, inactivate the X chromosome, but the remaining 26% of the samples were tumors of somatic organs (liver, brain, skin, heart, lungs and thyroid gland).

XIST.jpg

XIST expression is usually used to classify female oncological diseases, and the more surprising the results are: some types of tumors in men activate XIST and show signs of X inactivation. One possible explanation for this phenomenon is genetic instability: cancer cells often have multiple copies of chromosomes, and if two X chromosomes are accidentally located in the same cell, it may be necessary to inactivate one of them by activating XIST, regardless of whether this cell belongs to a female or male individual.

An important conclusion of the study is that there are probably several important genes in the X chromosome that, when suppressed, contribute to the growth of cancer. This will be the subject of study in future studies.

Article A.Sadagopan et al. Somatic XIST activation and features of X chromosome inactivation in male human cancers published in the journal Cell Systems.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru .

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