Cancer-causing mutations start years prior to diagnosis

The study was carried out by a team of international researchers

The study was carried out by a team of international researchers

Despite the extensive array of analytical approaches described in these new reports, the researchers were still unable to identify any driver mutations in 5% of the cancers in their study. This allowed the researchers to demonstrate that the some of the newly predicted driver mutations actually changed how genes were turned on or off - albeit in a small number of samples containing mutations in a given gene. Researchers from the Wellcome Sanger Institute in the United Kingdom are part of the team.

Their work produced a host of new discoveries - from the number and location of so-called driver mutations that push cells to reproduce uncontrollably, to the surprising similarities between cancers found in different types of tissue.

These findings take us "one step further down the road of understanding all the complexities of cancer", said Dr. William Cance, chief medical and scientific officer for the American Cancer Society. "For more than 30 cancers, we now know what specific genetic changes are likely to happen, and when these are likely to take place".

"With the knowledge we have gained about the origins and evolution of tumours, we can develop new tools and therapies to detect cancer earlier, develop more targeted therapies and treat patients more successfully", said Lincoln Stein of the project steering committee, in a statement released by the Ontario Institute for Cancer Research.

Until now, previous studies focused on the 1% of the genome that codes for proteins.

Previous published studies-such as those from the US -funded Cancer Genome Atlas (TCGA)-originally looked only at the "exome", protein-coding DNA that make up just 1% of the genome, of tumors because it was cheaper and easier. Such analysis includes all the ways DNA and RNA influence our personal biology. The results of this coordinated effort have now been published in a series of nearly two dozen papers.

The Cancer Atlas aims to provide a personalised journey for the diagnosis and treatment of every patient.

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They discovered traces of 23 different virus types in 356 cancer patients.

The results reveal that there are thousands of combinations of mutations within and between individual cancers, as well as more than 80 mutation-causing processes, some age-related, others inherent, as well as linked to lifestyle choices such as smoking and drinking. Some reflect the lifestyles that people have engaged in. Findings from the new study were published recently in Nature through an article titled "The evolutionary history of 2,658 cancers". The important thing is to figure out which mutations are key to cancer. It also provides important new information about the order in which these mutations accumulate during cancer development.

"This shows that the window of opportunity for early intervention is much wider than we expected", Campbell said.

"The incredible work of the Pan-Cancer Project team that was unveiled today is the culmination of a remarkable global collaboration that has enriched our understanding and provided new ways to approach the prevention, diagnosis and treatment of cancer", said The Honourable Ross Romano, Ontario's Minister of Colleges and Universities. "This sequencing will not mean cancers are cured, but points us towards developing drugs for preventing and treating resistance once it arises", Campbell says.

Enormous variations were found, from very few in cancers seen in children, to up to 100,000 in samples of lung cancer. "We have highlighted the function of mitochondrial genes in oxidative phosphorylation, DNA fix and cell cycle, showing their connections with clinically actionable genes". The research was able to pinpoint numerous mutational signatures that give rise to the wild growth of cancer cells by finding the differences in the DNA sequence and gene expression between cancerous tumor cells and normal cells.

That day isn't here yet because genetic sequencing and computer processing costs remain too expensive to build up the sort of comprehensive genetic data that's required, Campbell said.

A massive worldwide effort has yielded multifaceted studies of more than 2,600 tumours from 38 tissues, generating a wealth of insights into the genetic basis of cancer.

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