Analysis of the entire tumor RNA picks up more clinically relevant genetic changes in childhood cancers than traditional diagnostic methods, new research has shown.
A piece of tumor tissue is taken from all children with cancer to determine the exact form of their disease. The piece of tissue is looked at under a microscope and analyzed for genetic faults.
Changes in both DNA and RNA can provide clues about the exact cancer type, the aggressiveness of the tumor, and the possible benefit of targeted drugs.
All available RNA in a piece of tumor tissue from every child with cancer in the Netherlands is studied using so-called ‘RNA sequencing,’ in addition to traditional diagnostics. This is done through the Princess Máxima Center for pediatric oncology, the research hospital where children with cancer in the Netherlands are treated.
In some children, RNA sequencing has already led to improved diagnosis and adapted treatment. For a large number of cancer types, the diagnostic lab in the Princess Máxima Center has already replaced the traditional tests with broad RNA analyses. The researchers expect that they will also be able to switch completely quickly for the other cancer types—especially forms of leukemia.
In a new study, scientists at the Princess Máxima Center compared the effectiveness of RNA sequencing with traditional methods that allow you to specifically search the DNA and RNA for known gene changes. The study was published in the journal JCO Precision Oncology.
“RNA sequencing was already used before, but only in children who were very ill, and for whom standard treatment had stopped working,” says Bastiaan Tops, PhD, head of the Diagnostic Lab at the Princess Máxima Center for pediatric oncology, and co-leader of the study. “In our research hospital setting at the Princess Máxima Center, we have implemented RNA sequencing into standard diagnostics. Our new study shows that this approach is paying off.”
The team analyzed tissue samples from 244 children who were suspected of cancer and referred to the center between late 2018 and mid-2019. They focused on picking up fusion genes – a kind of genetic fault where two separate genes together form one new, faulty gene. Such fusion genes are found in many cancers and can often influence treatment decisions.
Using RNA sequencing, the team picked out a total of 78 fusion genes, which was 40% more than they found using traditional techniques.
In almost a third of the 23 RNA sequencing specific gene fusions, the finding led to a more accurate diagnosis or possible treatment. For a third of the 23 abnormalities ‘missed’ by traditional diagnostics, no specific tests currently exist.
“In this study, we show that a single test that searches the entire tumor RNA is almost one and a half times more sensitive to genetic faults in childhood cancer. I expect that the test we have developed will replace the various traditional methods in the foreseeable future,” says Patrick Kemmeren, PhD, group leader and head of the Big Data Core at the Princess Máxima Center for Pediatric Oncology, and co-leader of the study.
