Single trial for all children with cancer improves manageability

RNA sequencing, has been used on all children with cancer in the Netherlands since the opening of the Princess Mxima Pediatric Cancer Centre.

In the past six months, seven children were diagnosed with improvement or adaptive treatment through RNA sequencing.

A portion of tumor tissue is taken from all children with cancer to determine their exact form of the disease. Tissue fragments are examined under a microscope but also analyzed for genetic errors.

Changes in both DNA and RNA, the translation of the DNA code, can provide important clues about the exact type of cancer, how dangerous it is, and the possible benefits of targeted drugs. .

All available RNA in a sample of tumor tissue from every child with cancer in the Netherlands is studied using so-called RNA sequencing, which is now beyond traditional diagnosis.

This was made possible by opening the Princess Maxima Pediatric Cancer Center in 2018, the research hospital where all children with cancer in the Netherlands receive treatment.

RNA sequencing has improved diagnosis and adaptive treatment in some children. For many types of cancer, the Diagnostic Laboratory at Princess Maxima Center has replaced traditional tests with comprehensive RNA analyses.

The researchers hope that they will also be able to switch completely quickly to other types of cancer – 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 DNA and RNA for known gene changes . The study was published in the journal JCO Precision Oncology and is sponsored by NWO, KiKa and Adesium Foundation.

Once cancer was suspected, the team analyzed tissue samples from 244 children who were transferred to the Princess Maxima Center between late 2018 and mid-2019. They focused on picking out a so-called fusion gene – a type of genetic error in which two separate genes together form a new faulty gene. Such fusion genes are found in many cancers and can often influence treatment decisions.

Using RNA sequencing, the team selected a total of 78 fusion genes. That number is 23 or 40% more than they found using traditional techniques. Traditional methods have found another 55 fusion genes, but usually only one of them is selected from the fusion process, while information from both genes can be important for diagnosis or treatment.

This finding leads to a more accurate diagnosis or the possibility of treatment in nearly a third of the 23 RNA sequence-specific gene fusions. In the case of a girl, the pathologist’s diagnosis was modified based on RNA sequencing for neonatal fibrosarcoma, a soft tissue tumor, with so-called NTRK fusion. This means she may receive a new targeted drug as part of a clinical trial.

The one-year-old boy’s diagnosis of a brain tumor ranged from glioblastoma to hemispheric glioma, a tumor with a less bad outcome. When the standard treatment stopped working, he was given a precision drug that stabilized him for another year.

There is currently no specific test for a third of the 23 abnormalities that are “missed” by the traditional diagnosis. For other missed gene changes, technical reasons play a role – or related testing is not required because it does not appear to be related to tumor type.

Dr Bastiaan Tops, head of the Diagnostic Laboratory at Princess Maxima Pediatric Cancer Center and co-leader of the study, said:

‘RNA sequencing has been used before, but only in very sick children and standard treatment has stopped working. We have made RNA sequencing the standard diagnosis in our research hospital at the Princess Maxima Center.

‘Because we can look at the entire genetic context of a child’s tumor at diagnosis, we can discuss the possible consequences of treatment with the child’s doctor. young immediately. That means we can give children with cancer the best opportunities, based on the latest scientific insights. ‘

Dr Patrick Kemmeren, team leader and head of Big Data Core at Princess Maxima Pediatric Cancer Center and co-leader of the study, said:

‘In this study, we show that a single test that searches for the entire tumor RNA is almost one and a half times more sensitive to genetic errors in childhood cancer. I hope that the test we have developed will replace the various traditional methods in the near future.

“In my group, we conduct a much broader study of DNA and RNA abnormalities in childhood cancers. If we detect new abnormalities, they can also be inserted right into the cancer cells. new diagnoses – and even retrospectively examined in children under treatment.

This way, children with cancer benefit as quickly as possible from the new findings in basic research. ”

Source: Medindia

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