Cancer cells are masters of camouflage: They mutate, hide, and thus evade therapies. Researchers at the University of Münster are therefore studying the genetic secrets of tumors. Their goal: to discover how cancer cells develop in the body, defy therapies, and cause relapses. This includes Dr. Marcel te Vrugt and Gerrit Randau, both from Pediatric Hematology and Oncology, as well as Priv.-Doz. Dr. Sarah Sandmann-Varghese from Medical Informatics. The interdisciplinary trio has developed a new method to detect cancer cells hiding in lymphatic tissue, blood, and bone marrow and to understand their strategies. For this project, the team has now been awarded the Young Researcher Award, endowed with 2,500 euros, from the German Childhood Cancer Foundation and the Society for Pediatric Oncology and Hematology (GPOH).

The trio investigated two specific cancers of the lymphatic system: T-cell lymphoblastic lymphoma (T-LBL) and acute T-cell lymphocytic leukemia (T-ALL). While T-LBL is primarily confined to lymph nodes and other lymphatic organs, T-ALL spreads to the blood and bone marrow. Despite their differences, the two diseases are genetically related. The team analyzed samples from children and adults with T-LBL and T-ALL at diagnosis and at relapse. They also examined healthy tissue to identify mutation patterns specific to each disease, allowing for individualized treatment.

The focus was on so-called clonal evolution. This describes how tumor cells undergo genetic change over the course of the disease, how new mutations arise, and how certain cell groups – so-called clones – dominate or disappear. "We discovered that certain genetic patterns are typical for both diseases," explains te Vrugt. Using bioinformatics methods, the "family trees" of the genetic changes were reconstructed. This allows us to understand how tumor cells respond to therapies and why some mutations only appear during a relapse.

An important part of the research was the combination of two genetic analysis methods: bulk next-generation sequencing, which can detect small changes in the genome, and SNP arrays, which enable the detection of larger structural variations such as the absence or addition of entire DNA segments. By calculating the "cancer cell fractions" – the proportion of tumor cells with a specific mutation – it is possible to combine the results from the analysis of these different data types. "With our method, we can place this combined information on genetic variants in a temporal context and reconstruct the clonal evolution of the tumor," explains Sandmann. "This allows us to understand complex tumor development with many mutations and identify evolutionary trajectories, i.e., sequences of mutations specific to a group of diseases."

The trio sees great potential in the analysis of clonal evolution: "We hope to be able to examine even more patients in the future," says Gerrit Randau. "In the long term, our work could contribute to deciphering the genetic characteristics of the diseases. Our goal is to identify risk groups among our patients as early as possible and improve their treatment." The GPOH is the central scientific professional society for the treatment of cancer in children and adolescents in Germany. For the fifth time, the GPOH has awarded the Young Researcher Award, which recognizes outstanding research in pediatric oncology.