'Genetic brake' for disease

Monday April 20 2009

The Daily Express has reported on a “new treatment to halt tumours”. It said research had discovered the ‘brake’ to slow down and even stop cancer. The newspaper reported that British scientists had worked out how cancer develops through a “complex network of genes dictating whether or not healthy cells turn cancerous”. The research will also be used to fight multiple sclerosis.

This news story is based on a complex genetic study that found that certain abundant elements in DNA (repetitive elements) - previously thought to play a limited role - may be more involved than once thought in turning on the decoding of genes in cells. As reported, these are significant findings and could have implications for our understanding of how diseases such as cancer develop.

However, it is too soon to suggest the study found cancer ‘brakes’ or that there is a new treatment. At best, this connection is still hypothetical, as this study did not make direct links between tumour development and the activity of these      DNA elements.

Where did the story come from?

The study was carried out Dr Geoffrey Faulkner and colleagues from the University of Queensland, Australia, RIKEN Yokohama Institute in Kanagawa, Japan, the Dulbecco Telethon Institute in Rome and Naples, Griffith University in Australia and the University of Edinburgh. The researchers are supported through various grants and fellowships from government and academic organisations in their countries.

The study was published in the peer-reviewed medical journal, Nature Genetics .

What kind of scientific study was this?

This laboratory study is part of a larger study (called FANTOM4), which is investigating the properties and function of particular elements of DNA. There are several types of repetitive elements, including retrotransposons, which together make up a large proportion of DNA in mammals (30-50% according to the researchers). All of these repetitive elements are important for DNA structure.

Although most repetitive elements do not appear to do anything in the cell, they can, in some cases, play a role in switching on gene expression (how the information from a gene is used to make a functional gene product, such as a protein). The activity of retrotransposons is of particular interest to researchers because when they are inserted incorrectly into genes, they can cause mutations that lead to disruptions in genetic expression and subsequent disease.

The researchers in the study looked at different tissues from mice and humans. They were interested in profiling regions of DNA where gene expression begins (called transcription start sites or TSS) and investigating whether these regions were located  in retrotransposons.

To do this they used a technology called Cap Analysis Gene Expression (CAGE); a method of tagging the genome at places where gene expression (decoding) begins. This was a complex tagging task that involved mapping 65 million human and 18.5 million mouse CAGE tags.

The researchers were also interested in precisely what type of gene expression happens when initiated within retrotransposons.

They also carried out a series of complex experiments that investigated the association of transcription start sites in retrotransposons and other areas of the DNA that are involved in gene expression.

What were the results of the study?

The human tissue had 44,264 transcription start sites that had their basis in a repetitive element (18% of all TSS in the human genome). In mice, this number was 275,185 (31% of all TSS in mice). In spite of these high numbers though, the researchers noted that transcription start sites in retrotransposons themselves were expressed less than those in TSS from non-repetitive elements.

The expression of these repetitive elements varied across different tissue types: the clearest pattern was seen in human embryonic tissue where 30% of all the CAGE tags were associated with these. In other tissues including fat, brain, liver and testis, the pattern was less clear.

The researchers say their study confirms that retrotransposons are important components of regions of the genome that turn on transcription, that they are tissue specific and that they predominantly have a role in gene expression in the nucleus of the cells (rather than in the cytoplasm).

What interpretations did the researchers draw from these results?

The researchers say that retrotransposons are “multifaceted regulators of the functional output of the mammalian transcriptome”, i.e. they play an important role in regulating gene expression. They expect there will be extensive follow-up research to their study.

They add that it was previously believed gene expression was controlled by a small number of master, or regulator, genes. This research reveals there are hundreds of these types of genes, all interacting in tens of thousands of ways.

What does the NHS Knowledge Service make of this study?

The main finding of this complex genetic study is that there appears to be a “sophisticated network of regulatory elements” involved in how cells behave in the body, including potentially, the cells that are involved in the development of disease. This is in contrast to the previous belief that these diseases may be linked to faulty regulation by certain ‘master’ cells.

Retrotransposons are known to play a role in gene expression and can be found in a broad range of cells. As such, these elements of the genome are thought to potentially be involved in the development of cancer.

At present, this research does not signify a “new treatment to halt tumours” as reported in the Daily Express. However, these are exciting findings for the scientific community and although it is too early to suggest that cancer ‘brakes’ have been discovered, these promising findings will undoubtedly lead to further research in this area.

Analysis by Bazian
Edited by NHS Choices