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Number of mutations needed to cause cancer calculated

19 October 2017
Appeared in BioNews 923

Between one and 10 mutations are required for a healthy cell to turn cancerous.

Researchers from the Wellcome Trust Sanger Institute developed a novel evolution-based method to assess how many of the thousands of mutations found in cancer cells are necessary to drive cancer development.

'We have addressed a long-standing question in cancer research that has been debated since the 1950s: how many mutations are needed for a normal cell to turn into a cancer cell? The answer is – a small handful,' explained Dr Peter Campbell of the Wellcome Trust Sanger Institute, and lead author of the study.

The idea behind the study, published in Cell, was that cancer cells are subject to evolutionary pressures, including positive selection. This means that mutations providing an advantage for the survival of the cancer cell should be found more often in tumours than 'neutral' mutations, which do not influence the cancer cells' survival.

In the study, the researchers analysed mutations in over 7600 tumours from 29 different types of cancers. They found that the number of so-called 'driver mutations' that lead to the development of a cancerous cell varied widely between different types of cancer.

Nearly all coding mutations found in cancer cells – around 99 percent - were actually harmless and can be tolerated by the cell without affecting its survival. Yet just a few specific mutations could drive cancer.

'For example, about four mutations per patient on average drive liver cancers, whereas colorectal cancers typically require 10 or so driver mutations,' said Dr Campbell.

In addition to this, around half of the identified driver mutations were found in genes that had not previously been implicated in cancer development, highlighting the need for wider research into the genetic basis of cancer.

The researchers hope their findings may lead to the development of a more personalised approach to cancer treatment in the future, depending on which mutations are present in the patient’s tumour.

Speaking to the BBC, Dr Nicholas McGranahan from Cancer Research UK and UCL Cancer Institute called the approach 'elegant', but cautioned: 'This study focuses on one part of cancer evolution, it can only give us insight into part of the puzzle. Other components such as how DNA is packaged into chromosomes are also key in how a tumour progresses and will need to be looked at to give us a clearer picture of how cancer evolves.'

Evolutionary Analysis Reveals Number, Nature of Mutations Under Positive Selection in Cancer
GenomeWeb |  19 October 2017
'Handful of changes' make cancer
BBC News |  19 October 2017
One to 10 mutations are needed to drive cancer, scientists find
Science Daily |  19 October 2017
Universal patterns of selection in cancer and somatic tissues
Cell |  19 October 2017
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