Genome 'atlas' pinpoints driver mutations that cancers share

The study was carried out by a team of international researchers

However, at this stage, the results can not be used to test for cancers in people.

Getz added that knowing where these non-coding drivers reside in the genome - mainly in the regulatory regions - could help focus future studies on these regions. Over our lifetime these mutations build up and cells may be mis-programmed, leading to cancer.

To grow and spread, cancer cells take a number of genetic steps to overcome the normal cell controls that allow them to enhance their growth rate, move into nearby tissues and evade our immune system.

The U.S. National Cancer Institute has more about cancer genetics. Yet now, investigators at EMBL's European Bioinformatics Institute (EMBL-EBI) and the Francis Crick Institute have analyzed the whole genomes of over 2,600 tumors from 38 different cancer types to determine the chronology of genomic changes during cancer development.

For the new analysis in the journal Nature, more than 700 researchers examined more than 2,600 samples from 38 cancer types.

Causes of cancer are being catalogued through an global study revealing the genetic fingerprints of DNA-damaging processes that drive cancer development.

However, by generating new genetic changes, APOBEC3B can also drive cancer evolution and help cancer cells become resistant to chemotherapy. However, the shortcut has left out many changes that may trigger cancer development. Relatively few RNA splicing genes contain cancer driver mutations in their coding sequences, but many are affected by noncoding mutations.

The discovery involves areas of DNA that do not directly code for the proteins that carry out cellular activities, but instead control how genes are switched on and off. Scientists have long understood that these noncoding regions play an important role in cancer, but describing that role has been formidably hard. "I congratulate the entire research group on this ground-breaking achievement in cancer research".

Some countries, such as the United Kingdom, are moving toward whole-genome sequencing of every cancer patient's tumor to guide treatment; the full cost is still thousands of dollars per genome, Campbell says.

"We are finding that cancer represents the far end of an enormous spectrum of change", said Campbell.

They discovered traces of 23 different virus types in 356 cancer patients. Unlocking these patterns and understanding the timelines of genetic mutations means it should now be possible to develop new diagnostic tests, that pick-up signs of cancer much earlier.

"Although cancer is caused by changes in an organism's DNA, these changes also manifest via RNA", says Alvis Brazma, Functional Genomics Senior Team Leader and Senior Scientist at EMBL-EBI.

The researchers found that most driver mutations are in the DNA that codes for proteins. The result is the largest database of reference mutational signatures ever. We had previously identified 21 main types of signatures in pancreatic cancer for example, but work on the Cancer Atlas has revealed 90.

The team found these mutations occurred "particularly early" in ovarian cancer as well as two types of brain tumours. This uniqueness is a huge advantage when a patient presents with a cancer that has moved or metastasized. But many driver mutations are relatively rare and are missed by this approach. These genetic signatures made cancer cells vulnerable to treatment with immune checkpoint blockade, a major strategy in immunotherapy.

This unprecedented level of data crowd-sourcing means researchers, clinicians and industry can now work together, anywhere across the globe. "It's the vision we all want to get to", Campbell says.

In another study in Nature, researchers studied the molecular processes that cause cancer mutations, including those that damage DNA and others that, when broken, fail to properly fix DNA.

Most of our understanding of this process comes from the sets of genetic instructions for building the body's proteins. The effort picked out driver mutations in this part of their genome, and helped doctors make more specific diagnoses about what kind of cancers patients had. If the gene mutations are detected early on, more people will survive and tackle cancer through early treatment.

The Australian research groups involved include the University of Melbourne, Peter MacCallum Cancer Centre, QIMR Berghofer, Garvan Institute, University of Queensland and the Melanoma Institute of Australia.



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