Cancer Mutations more commonly hit X Chromosome

A recent study looks at how cancer mutations often affect the x chromosome.

As the study authors note that cancer originates from a individuals genetic material, "somatic mutations" from individual cells during an individual's lifetime often accumulate over time, according to lead study author Professor Roland Eils, who leads bioinformatics departments both at DKFZ and Heidelberg University.

The researchers looked and when and where the mutations occurred in the hopes that they could gain insights into early mechanisms involved for sending cells along a pathway to cancer.

The study notes the following, courtesy of a press release: "In the current study, the researchers analyzed the genome sequences of more than 400 tumors from patients suffering from twelve different types of cancer, including brain cancer in children and adults, leukemias and breast cancer.

"The scientists were surprised to find that mutations were extremely frequent in the X chromosome of females, which is responsible for determining sex. In many cancers, this chromosome displayed from two to four times as many mutations as were observed in the other chromosomes. Every cell in a female has two copies of the X chromosome and interestingly the rate was not the same in the two copies. From embryonic development onwards, one of the copies is inactivated in each cell. The higher mutation rate exclusively affects the inactive copy.

"This phenomenon was not found in male cancer patients, whose cells carry only one X chromosome, or in inactive X chromosomes of healthy female cells. And in rapidly growing tumors, mutations were found to be particularly frequent in the inactive X chromosome. The researchers also discovered that the build-up of mutations occurs at a very early stage of carcinogenesis."

While prior studies have shown that DNA duplication existed in the original form of the cell, the inactive x chromosome also shows that it is always the last to be duplicated.

Our theory is that cells which have accidentally undergone a growth-promoting mutation experience a state of stress caused by the rapid cell division," said Natalie Jäger, first author of the article, via the release. "They may not have enough time to repair errors, or they may lack enough of the building blocks necessary to create DNA. These problems mainly affect genomic regions that are duplicated at a late stage such as the inactive X chromosome."

More information regarding the study can be found via the journal Cell.