British researchers have explained the way cancers make a chaotic mess of their genetic code in order to thrive.
Cancer cells can differ hugely within a tumor – it helps them develop ways to resist drugs and spread round the body.
A study in the journal Nature showed cells that used up their raw materials became “stressed” and made mistakes copying their genetic code.
Scientists said supplying the cancer with more fuel to grow may actually make it less dangerous.
Most normal cells in the human body contain 46 chromosomes, or bundles of genetic code. However, some cancerous cells can have more than 100 chromosomes.
And the pattern is inconsistent – pick a bunch of neighboring cells and they could each have different chromosome counts.
This diversity helps tumors adapt to become untreatable and colonize new parts of the body. Devising ways of preventing a cancer from becoming diverse is a growing field of research.
Scientists at the Cancer Research UK London Research Institute and the University College London Cancer Institute have been trying to crack how cancers become so diverse in the first place.
It had been thought that when a cancer cell split to create two new cells, the chromosomes were not split evenly between the two.
However, lead researcher Prof. Charles Swanton’s tests on bowel cancer showed “very little evidence” that was the case.
Instead the study showed the problem came from making copies of the cancer’s genetic code.
British researchers have explained the way cancers make a chaotic mess of their genetic code in order to thrive
Cancers are driven to make copies of themselves, however, if cancerous cells run out of the building blocks of their DNA they develop “DNA replication stress”.
The study showed the stress led to errors and tumor diversity.
Prof. Charles Swanton said: “It is like constructing a building without enough bricks or cement for the foundations.
“However, if you can provide the building blocks of DNA you can reduce the replication stress to limit the diversity in tumors, which could be therapeutic.”
He admitted that it “just seems wrong” that providing the fuel for a cancer to grow could be therapeutic.
However, he said this proved that replication stress was the problem and that new tools could be developed to tackle it.
Future studies will investigate whether the same stress causes diversity in other types of tumor.
The research team identified three genes often lost in diverse bowel cancer cells, which were critical for the cancer suffering from DNA replication stress. All were located on one region of chromosome 18.
An international scientific team has published the most detailed analysis to date of the human genome.
The scientists have discovered a far larger chunk of our genetic code is biologically active than previously thought.
The researchers hope the findings will lead to a deeper understanding of numerous diseases, which could lead to better treatments.
More than 400 scientists in 32 laboratories in the UK, US, Spain, Singapore and Japan were involved.
Their findings are published in 30 connected open-access papers appearing in three journals, Nature, Genome Biology and Genome Research.
An international scientific team has published the most detailed analysis to date of the human genome
The Encyclopedia of DNA Elements (Encode) was launched in 2003 with the goal of identifying all the functional elements within the human genome.
A pilot project looking at 1% of the genome was published in 2007.
Now the Encode project has analyzed all three billion pairs of genetic code that make up our DNA.
They have found 80% of our genome is performing a specific function.
Up to now, most attention has been focused on protein-coding genes, which make up just 2% of the genome.
Genes are small sections of DNA that contain instructions for which chemicals – proteins – they should produce.
The Encode team analyzed the vast area of the genome sometimes called “junk DNA” because it seemed to have little function and was poorly understood.
Dr. Ewan Birney, of the European Bioinformatics Institute in Cambridge, who led the analysis, said: “The term junk DNA must now be junked.
“It’s clear from this research that a far bigger part of the genome is biologically active than was previously thought.”
The scientists also identified four million gene “switches”. These are sections of DNA that control when genes are switched on or off in cells.
They said the switches were often a long way along the genome from the gene they controlled.
Dr. Ewan Birney said: “This will help in our understanding of human biology. Many of the switches we have identified are linked to changes in risk for conditions from heart disease to diabetes or mental illness. This will give researchers a whole new world to explore and ultimately, it’s hoped, will lead to new treatments.”
Scientists acknowledge that it is likely to be many years before patients see tangible benefits from the project.
But another of the Encode team, Dr. Ian Dunham said the data could ultimately be of help in every area of disease research.
“Encode gives us a set of very valuable leads to follow to discover key mechanisms at play in health and disease. Those can be exploited to create entirely new medicines, or to repurpose existing treatments.”
British scientists have discovered another eight pieces of genetic code linked to osteoarthritis, bringing the total number to 11.
Inherited factors account for at least half of any individual’s chance of developing this common condition that affects the joints, experts believe.
And understanding these factors could offer up new treatments.
The research in The Lancet compared the DNA of 7,400 UK osteoarthritis patients with that of 11,000 healthy volunteers.
This allowed scientists to find the most promising “culprit” regions of the genetic code to study in more detail.
They repeated their work in another group of 7,500 people with osteoarthritis and about 43,000 individuals without the condition from Iceland, Estonia, the Netherlands, and the UK.
British scientists have discovered another eight pieces of genetic code linked to osteoarthritis, bringing the total number to 11
The results confirmed the three previously reported gene variants and found a further eight linked to osteoarthritis.
Further work is now needed to pinpoint the actual DNA changes within the genetic regions to establish exactly how these changes lead to osteoarthritis.
The one with the strongest effect was situated in the region of the GNL3 gene which produces a protein with an important role in cell maintenance.
Three others were in DNA regions involved in the regulation of cartilage, bone development and body weight.
One of the lead scientists, John Loughlin, who is professor of musculoskeletal research at Newcastle University, said: “We know that osteoarthritis runs in families and that this is due to the genes that people pass on, rather than their shared environment.
“In this study we were able to say with a high degree of confidence which genetic regions are the major risk factors for developing osteoarthritis: the first time that this has been possible for this common yet complex disease. It’s an important first step.”
Prof. Alan Silman, medical director of Arthritis Research UK, the charity that funded the work, said: “Until we understand the cause of this complex disease, we cannot hope to find a cure. This is a major breakthrough in our understanding of osteoarthritis, which we hope will help us to unlock the genetic basis of the disease.”
Researchers from UK Medical Research Council’s Laboratory of Molecular Biology have succeeded in mimicking the chemistry of life in synthetic versions of DNA and RNA molecules.
The work shows that DNA and its chemical cousin RNA are not unique in their ability to encode information and to pass it on through heredity.
The work, reported in Science, is promising for future “synthetic biology” and biotechnology efforts.
It also hints at the idea that if life exists elsewhere, it could be bound by evolution but not by similar chemistry.
In fact, one reason to mimic the functions of DNA and RNA – which helps cells to manufacture proteins – is to determine how they came about at the dawn of life on Earth; many scientists believe that RNA arose first but was preceded by a simpler molecule that performed the same function.
However, it has remained unclear if any other molecule can participate in the same unzipping and copying processes that give DNA and RNA their ability to pass on the information they carry in the sequences of their nucleobases – the five letters from which the genetic code is written.
The classic double-helix structure of DNA is like a twisted ladder, where the steps are made from paired nucleobases (RNA is typically a single helix).
Researchers have succeeded in mimicking the chemistry of life in synthetic versions of DNA and RNA molecules
Philipp Holliger and a team of colleagues created six different DNA- and RNA-like molecules – xeno-nucleic acids, or XNAs – by replacing not the nucleobases but the sugar groups that make up the sides of the ladder.
“There’s a lot of chemistry that seeks to build alternative nucleic acids, and people have been modifying the bases, the sugars and the backbone, but what we were focusing on was the type of nucleic acid or polymers that would retain the ability to communicate with the natural DNA,” Dr. Philipp Holliger explained in an interview for the Science podcast.
Because the nucleobases themselves were the same as those of DNA and RNA, the resulting molecules were able to join with their natural counterparts.
The effect is similar to work recently published in Nature Chemistry, showing that another sugar-substituted DNA analogue could be made to pair up with DNA itself.
But the crucial point in creating a full “synthetic genetics” is a set of nucleic acids like DNA and RNA that can not only carry genetic information, but would also allow it to be changed and passed on – evolution and heredity.
That requires a set of helper molecules called polymerases, which, once DNA or RNA “unzip” and expose their genetic information, help create new DNA molecules from those instructions.
Dr. Philipp Holliger and his colleagues have developed polymerases that efficiently transcribe the code of their synthetic DNA to natural DNA and then from that back to another synthetic DNA.
The process of evolution was encouraged in the lab; one of their DNA analogues was designed to cling to a particular protein or RNA target, those that failed to do so were washed away.
As successive copies of those that stuck were made, variations in the genetic code – and the resulting structure the molecules took on – led to ever more tightly attached XNAs.
“We’ve been able to show that both heredity – information storage and propagation – and evolution, which are really two hallmarks of life, can be reproduced and implemented in alternative polymers other than DNA and RNA,” Dr. Philipp Holliger explained.
“There is nothing <<Goldilocks>> about DNA and RNA – there is no overwhelming functional imperative for genetic systems or biology to be based on these two nucleic acids.”
In an accompanying article in Science, Gerald Joyce of the Scripps Research Institute wrote that “the work heralds the era of synthetic genetics, with implications for exobiology [life elsewhere in the Universe], biotechnology, and understanding of life itself”.
But the work does not yet represent a full synthetic genetics platform, he pointed out. For that, a self-replicating system that does not require the DNA intermediary must be developed.
With that in hand, “construction of genetic systems based on alternative chemical platforms may ultimately lead to the synthesis of novel forms of life”.