New tumour sampling method significantly improves genetic testing for cancer treatment

A pioneering tumour sampling method that more accurately detects genetic alterations in tumours has been developed by researchers at The Royal Marsden NHS Foundation Trust, Francis Crick and Roche.

The test builds on DNA sequencing which we use to find mutations that can be susceptible or resistant  to a personalised therapy. The tumours are complex because they are often made up of genetically different groups of cells which  sit in different parts of the tumour.

Current sampling methods can miss this genetic diversity because they use tissue taken from just one small location in the tumour.

Initially, the concept of improved sampling was tested in lung and bladder cancers, where a simulation of improved sampling reduced misclassification rates in deciding whether a patient was suitable for immunotherapy from 20% to 2% and from 52% to 4%, in different cancer types when compared to current methods. 
 
Based on this finding, they developed a technique called representative sequencing, which builds a more accurate picture of a tumour’s genetics. This works by taking the majority of the tumour removed at surgery – tissue that is not currently sampled and is routinely discarded - and mixing it so that cells from different areas of the tumour are more evenly distributed. A sample is then taken from this mixture for its genetics to be profiled.

The researchers tested this new method in 12 patients with kidney, breast, colon, lung or skin cancer. Comparing the new and current methods, they found that representative sequencing gave far more consistent results, as it avoids the bias of looking at just one small part of the tumour tissue. Instead, the new method is able to capture information from a well-mixed representation of the whole tumour, meaning much more reliable data is collected.

The method, which was developed in partnership with researchers from The Royal Marsden, the Francis Crick and Roche published in Cell Reports is being further tested in a prospective trial of   500 tumours at The Royal Marsden in London to further establish its feasibility and utility. The researchers hope that, following successful results, it will be rolled out further.

“By equipping clinicians with more accurate information about a tumour, we hope our method will lead to patients and treatments being significantly better matched. Additionally, there is an opportunity for critical biological insights to be made by increasing the search space within each tumour,” says Samra Turajlic, Consultant Medical Oncologist at The Royal Marsden group leader at the Francis Crick.
 
Professor David Cunningham, Director of Clinical Research at The Royal Marsden, said, “The selection of patients who will benefit from cancer therapies remains a major challenge – some patients get excellent, long-lasting tumour control whereas other patients may suffer side effects but without benefit. This simple but ingenious revision to an established technique to analyse tumour DNA should facilitate a more personalised approach to the treatment of cancer patients.”
 
“This method is more accurate, has more reproducible results and has the same sequencing cost as the current technique. In fact, by introducing an extra, simple purification step, it could become much cheaper than the existing process. It could be a gamechanger for tumour sampling in hospitals and in research,” says Kevin Litchfield, lead author and bioinformatician in the Translational Cancer Therapeutics Laboratory at the Crick.
 

By equipping clinicians with more accurate information about a tumour, we hope our method will lead to patients and treatments being significantly better matched.

Samra Turajlic, Consultant Medical Oncologist at The Royal Marsden