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Ring-shaped cancer DNA lets tumors mutate and resist treatment

Cancer’s ring-shaped DNA lets tumors evolve too fast for treatments to keep up – turning the disease chemo-resistant, scientists say

  • Mutations to cancer DNA make it more difficult to treat 
  • University of California, San Diego discovered that much of cancer DNA is ring-shaped instead of double-helixed, like normal human DNA 
  • Its unusual shape makes it easier for DNA to evolve in response to attempted treatments and evade them  

‘Doughnut-shaped’ rings of cancer DNA make tumors more aggressive and resistant to treatment, scientists believe.

Circles of extrachromosomal DNA (ecDNA) are found abundantly in human tumor cells, according to researchers from the University of California, San Diego (UC San Diego). 

The shape is different to normal human DNA, which forms twisting double helixes of genetic material, similar in appearance to ladders.

As a result of its circular shape, cancer DNA is more ‘open’ and can respond and morph to evade the treatments that doctors attempt to use to kill the cells, according to University of California, San Diego, scientists.  

Scientists at the University of California, San Diego discovered that much of cancer’s DNA is in doughnut shapes (pointed out by arrows in this microscopic photo), making it hard to target

Bits of human DNA code are packed into cell nuclei by being tightly wrapped around clusters of protein complexes.

To read the genetic instructions, cells rely on enzymes to cut and move sections, making only part of the DNA accessible at any one time.

The researchers likened the process to ‘reading a partially opened scroll.’

But cancer cells share some similarities with bacteria, which contain circular DNA that is generally more accessible.

This ‘highly accessible’ shape provides more access points where genetic information can be quickly transcribed and expressed, allowing cells to generate large amounts of growth-promoting genes, the scientists said.

It also allows them to evolve more quickly and respond more forcefully to their changing environment and threats, such as chemotherapy and radiation, they added.

The research, published in the journal, Nature, comes from the University of California San Diego, the UC San Diego branch of the Ludwig Institute for Cancer Research, Stanford University and the Howard Hughes Medical Institute.

Dr Paul S Mischel, a professor at the UC San Diego School of Medicine Department of Pathology and co-senior author, said the discovery marks a ‘paradigm-shift’.

‘This unique shape in human cancer cells is quite unlike normal human DNA,’ he said. 

‘It really shines a new light on to the 3D organisation of the screwed-up cancer genome and epigenome, which now provides a mechanistic basis for understanding why certain tumor cells are so aggressive.’

The authors say ecDNA was previously thought to be rare but is now believed to be detected in nearly half of human cancers.

When the cells multiply, they parcel out ecDNA in a seemingly random way, which allows for more rapid evolution and genetic change than if they simply divided into genetically identical cells, the scientists said. 

Effectively, because the tumor cells have more unique DNA, a treatment that targets a genetic change detected in some cells might not be present in others, allowing them to survive the onslaught of a cancer drug.  

It’s not clear how frequently cancer becomes treatment resistant, but a 2014 review states that the phenomenon is becoming more common. 

And the more treatments cancer becomes resistant to, the the poorer a patient’s survival odds become. 

Understanding how its shape lets cancer evolve may help scientists develop better treatments to to target and keep up with the disease, the UC San Diego team hopes. 

Read more at DailyMail.co.uk



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