‘A handful’ of gene faults can turn a healthy cell cancerous

Fewer than 10 errors in the DNA inside cells are enough to drive development of a cancer, according to new estimates. 

Researchers at the Wellcome Trust Sanger Institute found that different types of cancer are triggered by a different number of genetic changes (mutations).

Professor Sir Mike Stratton, director of the institute, said the research shows that a small number of mutated genes are responsible for converting a single normal cell into a cancer cell. The specific genes that are affected vary according to cancer type.

Cancers evolve in a similar way to species, with some genetic faults helping the cell survive, and some holding it back or causing it to die.

Dr Nicholas McGranahan, an expert in cancer evolution from the Cancer Research UK Lung Cancer Centre of Excellence at the UCL Cancer Institute, said that using ideas from species evolution can help scientists work out the genetic faults that cause a cancer to grow.

The researchers looked at the patterns of genetic changes of 7,664 tumours spanning 29 types of cancer. They found that on average tumours have around 4 genetic faults that drive them. 

The results are published in the journal Cell.

Testicular and thyroid cancers were among those that needed the fewest faults to develop (less than 1 on average), while melanoma, bowel and endometrial cancers needed the most (more than 10 on average). 

“The most surprising finding from this research was that most genetic faults didn’t harm the cell but rather accumulated over time,” said McGranahan.

While it’s known that hundreds of genes can become faulty and fuel growing cancers, around half of the faults found in the study were in genes that haven’t yet been linked to cancer. 

Stratton said these genes will be the target of future studies. 

“This increasingly precise understanding of the underlying changes that result in cancer provides the foundation for the discovery and use of targeted therapies that treat the disease,” he said. 

Dr Peter Campbell, who led the study, said they had addressed a long-standing question. In relation to how many mutations are needed for a normal cell to turn into a cancer cell, “the answer is a small handful”, he said. 

McGranahan added that the ways cancers evolve are complex, and this focuses on one 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,” he said.