Mutations in cancer often affect the X chromosome

October 18, 2013

Every case of cancer originates from changes in a person's genetic material (mutations). These usually occur as "somatic mutations" in individual cells during an individual's lifetime, rather than being inherited from a person's parents. "Over time, the original damaged cell accumulates additional mutations, and it is still largely unknown why," says Prof. Roland Eils, who leads bioinformatics departments both at DKFZ and Heidelberg University.

By studying when and where mutations occur the researchers hope to gain insights into the early mechanisms that send along a pathway to . The new international study coordinated by Roland Eils has now for the first time analyzed the exact distribution of somatic mutations in the genomes of tumor cells of various . Mutations do not affect all regions of the genome to the same extent. It is known, for example, that the number of depends on the sequence of bases making up a gene and the frequency at which it is transcribed into RNA molecules.

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 .

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 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.

Prior to each , the DNA in the original cell is duplicated. The inactive X chromosome 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," says Natalie Jäger, first author of the article. "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."

Roland Eils adds: "This finding helps us understand how cellular stress accelerates the fatal process of carcinogenesis and thus contributes to an accumulation of ever more in a cancer cell."

Explore further: New mutations driving malignant melanoma discovered

More information: N. Jäger et al: Hypermutation of the inactive X chromosome is a frequent event in cancer. Cell 2013, DOI: 10.1016/j.cell.2013.09.042

Related Stories

New mutations driving malignant melanoma discovered

January 24, 2013

Two new mutations that collectively occur in 71 percent of malignant melanoma tumors have been discovered in what scientists call the "dark matter" of the cancer genome, where cancer-related mutations haven't been previously ...

Researchers develop software tool for cancer genomics

August 26, 2013

Researchers at the Medical College of Wisconsin (MCW) have developed a new bioinformatics software tool designed to more easily identify genetic mutations responsible for cancers. The tool, called DrGaP, is the subject of ...

Genetic errors identified in 12 major cancer types

October 16, 2013

Examining 12 major types of cancer, scientists at Washington University School of Medicine in St. Louis have identified 127 repeatedly mutated genes that appear to drive the development and progression of a range of tumors ...

Recommended for you

New class of RNA tumor suppressors identified

November 23, 2015

A pair of RNA molecules originally thought to be no more than cellular housekeepers are deleted in over a quarter of common human cancers, according to researchers at the Stanford University School of Medicine. Breast cancer ...

Batten disease may benefit from gene therapy

November 11, 2015

In a study of dogs, scientists showed that a new way to deliver replacement genes may be effective at slowing the development of childhood Batten disease, a rare and fatal neurological disorder. The key may be to inject viruses ...

Molecular clocks control mutation rate in human cells

November 9, 2015

Every cell in the human body contains a copy of the human genome. Through the course of a lifetime all cells are thought to acquire mutations in their genomes. Some of the mutational processes generating these mutations do ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.