(CTN News) – In cancer cells, X-Chromosome genetic anomalies allow them to grow and proliferate unchecked. Interestingly, researchers have discovered another difference between normal and cancer cells: the X chromosome, normally inactivated in only XX female cells, can also be inactivated in male-derived cancers. This work will be published in Cell Systems on Nov. 9.
According to normal development, one copy of the female X chromosome is inactivated randomly throughout the human body in order to balance gene expression between the sexes.
As a senior author at the Dana-Farber Cancer Institute, Srinivas Viswanathan, a cancer geneticist and medical oncologist, explains, “We wanted to find out if this process that occurs naturally in normal development gets wrong in genetically unstable cancer cells.
In the study, the team of researchers identified high expression of XIST (the gene that shuts down gene expression on the X chromosome) in about 4% of the male cancer samples analyzed using publicly available datasets comprising thousands of DNA samples from cancer patients throughout the world.
Although XIST is expressed in both sexes at very early stages of development, X inactivation is believed to occur later in development in a gender-specific manner.
Female cancer cells have previously been shown to lose the ability to turn off one of their X chromosomes, leading to an increase in X-linked gene expression, but this ability of X inactivation had only been studied on female cells.
Among the 4% of anomalous male cancer samples identified, 74% were from reproductive cancers already shown to inactivate the X chromosome, leaving 26% from other types of cancer. Cancers of the liver, brain, skin, heart, lungs, and thyroid were among those diagnosed.
Due to the fact that XIST is a transcript typically used to classify female cancers, we were very surprised by the result. Therefore, we wanted to ensure it was not the result of a annotation. Viswanathan notes, however, that some male cancers of diverse subtypes are activated by XIST and show features indicative of X inactivation.
There are caveats to working with these types of datasets.
These samples have been handled by many people, and therefore there is a greater possibility of human error,” said co-corresponding author Cheng-Zhong Zhang, a cancer biologist at the Dana-Farber Cancer Institute. In order to find controls, we must be creative in how we examine the data. This is the largest source of uncertainty for us.”
If two X chromosomes are present in one cell,
This phenomenon may be explained by genetic instability. then it may be necessary to inactivate one by activating XIST, regardless of whether this cell is found in a woman or a man.
According to Viswanathan, another possibility is that there may be some genes on the X chromosome that, when silenced, contribute to the growth of cancer.
“In some ways, sex is the ultimate biomarker because it divides the human population. However, we often overlook the possibility that genetic differences between the sexes can impact cancer prognosis and treatment response,” says Viswanathan.