Cambridge scientists start to unravel cancer’s secrets
Scientists at the Wellcome Sanger Institute in Cambridge believe they have made a major breakthrough in cancer and ageing research.
They have developed a new sequencing method to study changes in the DNA of any human tissue.
While genetic changes occur naturally in our cells as we age – in most cases causing no harm – certain mutations can set a cell on the path to cancer. While genome sequencing has been used for many years to understand how cancer develops, it has never been accurate enough to detect new mutations in non-dividing cells – the large majority – until now.
The Wellcome Sanger study, partly funded by Cancer Research UK, showcases a new approach called nanorate sequencing (NanoSeq), that can uncover changes in the DNA of all human tissues with unprecedented accuracy.
The research has also opened up the possibility that cell division isn’t the main driving force behind genetic changes, as previously assumed.
The team originally set out to improve an advanced sequencing method called duplex sequencing, through which DNA is read multiple times to locate errors in the data.
When searching for mistakes in the data it became clear they were gathered at the ends of DNA fragments and had other features that suggested flaws in how the DNA was being prepared for sequencing.
Spanning four years, the research focused on enhancements and improving accuracy until fewer than five errors per billion letters of DNA was achieved.
Dr Robert Osborne, an alumnus of Wellcome Sanger Institute who led the work, said detecting mutations that were only present in one or a few cells was “incredibly technically challenging”. But because of Nano Seq’s vastly limited errors researchers are “now able to accurately study somatic mutations in any tissue.”
Taking advantage of the technique’s improved sensitivity, researchers were able to compare the rate and pattern of mutation in both stem cells and non-diving cells in multiple human tissue types, which led to an unexpected discovery.
Analysis of blood cells revealed a similar number of mutations in slowly dividing stem cells and a more rapidly dividing population called progenitor cells.
The same pattern was confirmed in analyses of non-dividing neurons and rarely-dividing cells from muscle, which revealed that changes accumulate throughout life in cells without cell division, and at a similar pace to cells in the blood.
It is hoped the NanoSeq method will enable scientists to study the effects of carcinogens like tobacco or sun exposure on healthy cells, as well as discover and understand new harmful substances that may cause cancer.
NanoSeq will also make it easier to take and test samples from people. Instead of taking intrusive biopsies of tissue, cells can be collected simply by scraping the skin or swabbing the throat.