Single Test for All Kids With Cancer Improves Management

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The technique, RNA sequencing, has been used for all children with cancer in the Netherlands since the opening of the Princess Mxima Center for pediatric oncology.

In the past six months, seven children received an improved diagnosis or adapted treatment thanks to RNA sequencing.

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 the microscope but also analyzed for genetic faults.

Changes in both DNA and RNA, a translation of the DNA code, can provide important clues about the exact cancer type, the tumor’s aggressiveness, 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, currently in addition to traditional diagnostics.

This was made possible by opening the Princess Maxima Center for pediatric oncology in 2018, the research hospital where all children with cancer in the Netherlands are treated.

RNA sequencing has already led to improved diagnosis and adapted treatment in some children. For many cancer types, the Diagnostic Lab in the Princess Maxima Center has already replaced the traditional tests with comprehensive 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 Mxima 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 and was funded by NWO, KiKa and the Adessium Foundation.

After suspected cancer, the team analyzed tissue samples from 244 children referred to the Princess Maxima Center between late 2018 and mid-2019. They focused on picking up so-called 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. That was 23 or 40% more than they found using traditional techniques. Traditional methods did find the other 55 fusion genes, but often only one of the two genes was picked up from the fusion, while information from both genes can be important for diagnosis or treatment.

The finding led to a more accurate diagnosis or possible treatment in almost a third of the 23 RNA sequencing-specific gene fusions. In the case of one girl, the pathologist’s diagnosis was modified based on RNA sequencing to infantile fibrosarcoma, a soft tissue tumor, with a so-called NTRK fusion. This meant she was able to receive a new targeted drug as part of a clinical trial.

The diagnosis of a one-year-old boy with a brain tumor was changed from glioblastoma to hemispheric glioma, a tumor with a less bad outcome. When standard treatment stopped working, he was given a precision medicine that kept him stable for another year.

No specific tests currently exist for a third of the 23 abnormalities ‘missed’ by traditional diagnostics. For the other missed gene changes, technical reasons played a role – or the relevant test was not requested because it did not seem relevant for the tumor type.

Dr. Bastiaan Tops, head of the Diagnostic Lab at the Princess Maxima Center for pediatric oncology, and co-leader of the study says:

‘RNA sequencing was already used before, but only in children who were very ill and for whom standard treatment had stopped working. We have implemented RNA sequencing into standard diagnostics in our research hospital setting at the Princess Maxima Center.

‘Because we can look at the full genetic landscape of a child’s tumor at diagnosis, we can discuss possible consequences for treatment with the child’s doctor right away. That means we can offer children with cancer the very best opportunities, based on the latest scientific insights.’

Dr. Patrick Kemmeren, group leader and head of the Big Data Core at the Princess Maxima Center for Pediatric Oncology, and co-leader of the study says:

‘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.

“In my group, we conduct much broader research into DNA and RNA abnormalities in childhood cancer. If we discover new abnormalities, they can also be immediately included as part of new diagnoses – and even tested retrospectively in children who are already under treatment.

In this way, children with cancer benefit as quickly as possible from new findings within fundamental research.”

Source: Medindia



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