Medical researchers have discovered a new type of mechanism causing cancer susceptibility, showing that tiny changes in some anti-cancer genes can act as magnets to attract modifying "biochemical tags", effectively switching them off and predisposing families to an increased risk of the disease.
The study and its findings are reported in the leading international journal Cancer Cell.
The researchers, from the University of New South Wales (UNSW), believe a tiny spelling mistake involving a single letter in the DNA sequence near the start of the genes is what attracts the biochemical tag – known as methylation.
This biochemical tag directly impacts on our DNA, by switching genes off.
"Methylation sits on top of our DNA, and provides the instructions to turn the gene off," explains study co-leader, Dr Megan Hitchins, from UNSW's Lowy Cancer Research Centre.
In one well-known cause of hereditary cancer, changes in the cancer-prevention gene MLH1 are passed from parent to child creating up to 80 percent risk of developing bowel, uterine and other cancers. However, some families with hereditary cancer have no spelling mistakes in MLH1, but instead have methylation sitting on the gene.
"When the methylation attaches to the MLH1 gene in these families, it causes it to be completely switched off and as a consequence cancer develops," says study co-leader and head of the adult cancer program at the Lowy Cancer Research Centre, Professor Robyn Ward. "But until now, we did not understand how these methylation tags were being passed from parent to child."
In the study the researchers looked at three generations of a large family, who had cancer at a young age, but in whom no spelling mistakes typical of this hereditary cancer syndrome had been found. Strikingly several members of the family from all generations had methylation tags on their gene.
"In this family, biochemical tags attached to the MLH1 gene were present in all three generations. This was intriguing since these markers are usually removed during the production of eggs and sperm," Dr Hitchins said.
"What we found was that a subtle change near the gene was acting like a magnet to attract methylation. So it was not the methylation itself that was being passed from parent to child, but rather the DNA change, and this acted as a methyl magnet," she said.
The methylation was cleared away in the sperm and eggs and then recreated in each new generation, the researchers said.
Professor Ward said the discovery pinpointed the cause of cancer in this family and it offered new options for genetic diagnosis, counselling and early interventions in other families at risk of hereditary cancers.
The team is also exploring the use of certain drugs to clear away the methylation in cancer to switch the anti-cancer genes back on again. In the future these drugs may be used to create a more targeted approach to cancer treatment and possibly prevention.

DNA and RNA arrived from space.

For some reason or another, all of us like to believe that Earth is special - after all, our planet is the only one able to sustain life that we know of. Indeed, Earth is special in its own way, but life would not have been possible without the significant contribution of material coming form space. In fact, a new study shows that the compounds making up DNA and RNA actually originated in space, not on Earth as previously thought, and were brought here by meteorite fragments and other similar objects.

"Because meteorites represent leftover materials from the formation of the solar system, the key components for life - including nucleobases - could be widespread in the cosmos. As more and more of life's raw materials are discovered in objects from space, the possibility of life springing forth wherever the right chemistry is present becomes more likely," said Mark Sephton, professor of Earth science and engineering at Imperial College London and co-author of the study."We believe early life may have adopted nucleobases from meteoritic fragments for use in genetic coding which enabled them to pass on their successful features to subsequent generations," said the leader of the study, Zita Martins of the Department of Earth Science and Engineering at Imperial College London.

In 1969, a meteorite fragment, known today as the Murchison meteorite, crashed in the Australian outback. A thorough analysis, following its discovery, showed that it contained uracil and xanthine molecules (nucleobases), which are building blocks for genetic materials made up of a heavy carbon isotope. On Earth, such molecules contain only light carbon isotopes.

However, these two molecules are just a few of many others found in the respective fragment. "There are about 70 different amino acids in the Murchison meteorite. About six or so are the same kinds of amino acids associated with life on Earth," said David Deamer from the University of California.

The uracil molecule is one of the four bases for the RNA molecule, therefore it is invaluable to life. Deamer points out that, although these molecules have been proven to originate in space, they could have been developed on Earth just as well. Nevertheless, the proportion of molecules originating only in space or only on Earth is currently unknown.

"We don't know the answer yet. Most people would say that both contributed to the organic compounds available on Earth, but we don't know with certainty how much of one compared to the other," said Deamer.

between 3.8 and 4.5 billion years ago, when primitive life first appeared, the Earth and Mars could have been literally bombarded with meteorites similar to the Murchison, thus studying the impact they would have had on different planets could reveal how life evolved in the solar system.

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