With the help of molecular tumor diagnostics, cancer medicine is able to filter out individual cancer properties, in order to recommend the most promising and potentially successful treatment options to patients. However, just how reliable such prognoses are also depends on the spatial distribution of the tumor markers inside a tumor. A current study by scientists at the German Cancer Consortium (DKTK) at the University Hospital Düsseldorf shows that for children's brain tumors a single tissue sample suffices in order to make reliable prognoses using gene activity patterns. Comparatively, genetic markers are usually too unevenly distributed in the tumor, thus making several biopsies necessary, the study shows. The DKTK combines the German Cancer Research Center in Heidelberg as the core center together with various university locations across Germany with a specific oncological focus.

Molecular patterns are being used more and more frequently in brain tumors to predict the response to cancer therapy and help find the best possible treatment for the patient. "With children's brain tumors, so called medulloblastoma, the prognoses are quite reliable in many cases," explains Dr. Marc Remke, who leads the junior group for pediatric neurooncology at the German Cancer Consortium (DKTK) at the University Hospital of Düsseldorf. "If for example the so–called Wnt signaling pathway is activated in the tumor, patients with the most common standard therapies have an excellent chance of recovery." Since 2016, these and other molecular classifications of brain tumors have also been recognized by the World Health Organization (WHO).

The prerequisite for the reliability of the methods, however, is clearly determining the genetic tumor profile. Herein lies the challenge, as the cells of a brain tumor often have more differences than similarities, as Marc Remke found together with his Canadian colleagues from the University of Toronto, the Hospital for Sick Children, and the Cancer Agency British Columbia. The team showed for the first time that high grade gliomas as well as medulloblastomas consist of genetically different regions. The researchers dissected tumor samples from a total of 35 patients and examined the spatial distribution of genetic changes which play a role in tumor development. "The different tumor regions differ by the individual mutation and the copy number of certain genes in the DNA of the cancer cell," explained Remke. "Both in the case of child medulloblastomas as well as for as well as with gliomas, two or more biopsies would be necessary in order to determine whether the genetic changes are present in the entire tumor."

The discovery that brain tumors are not a homogenous unit on a genetic level has considerable consequences for the development of new targeted therapies. "Molecular target structures that are the target of therapeutic agents should be present in all tumor cells, as this lowers the likelihood that resistances will develop. This way we can grab the tumor by the root and spare patients additional biopsies," emphasized Remke.

The study identifed the activity of cancer relevant genes, such as the Wnt signaling pathway, as particularly homogeous and therefore promising tumor markers. "With the medulloblastomas, the activity patterns of the genes we examined were comparable in all tumor regions and a single biopsy was enough to form a reliable prognosis," said Remke.

Currently, the researchers are studying whether there are further molecular changes in cancer which occur in all tumor regions. "We have early indications that so–called epigenetic factors, chemical groups in the DNA, could be interesting for the diagnostics of brain tumors," said Remke, summarizing initial findings.

The article, "Spatial heterogeneity in medulloblastoma," was published in the journal Nature Genetics.