A holistic tumor sampling method that more accurately detects genetic alterations in tumors has been developed by researchers from the Crick, Roche and The Royal Marsden NHS Foundation Trust. The study was published in Cell Reports.
Initially, the researchers tested improved sampling 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% respectively, when compared to current methods.
Based on this finding, the researchers developed a technique called representative sequencing, which builds a more accurate picture of a tumor’s DNA. This works by taking the majority of the tumor removed at surgery—tissue that is not currently sampled and is routinely discarded—and mixing it so that cells from different areas of the tumor are more evenly distributed. A sample is then taken from this mixture to be DNA sequenced.
The researchers tested the method in 12 patients with kidney, breast, colon, lung or skin cancer. Comparing 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 tumor tissue. The new method captures information from a well-mixed representation of the whole tumor.
The method is being further tested in 500 tumors at The Royal Marsden in London to determine its feasibility and utility.
“By equipping clinicians with more accurate information about a tumor, 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 tumor,” Samra Turajlic, group leader at the Crick and consultant medical oncologist at The Royal Marsden, said in a statement.
Through extensive testing on a case of kidney cancer, the representative sampling method gave identical genetic results 95% of the time, compared to only 77% consistency with the current methods. Similarly, in a case of skin cancer, the new method correctly identified a highly complex and difficult to treat cancer from the outset, whereas the current method missed important genetic information.
“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 tumor sampling in hospitals and in research,” Kevin Litchfield, lead author and bioinformatician in the Translational Cancer Therapeutics Laboratory at the Crick, said in a statement.
