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Cancer DNA in the blood: an early warning system for recurrent tumors in children

No. 15 | 16/03/2022 | by Koh

Neuroblastomas release DNA fragments into the blood and cerebrospinal fluid of patients. These genetic material can indicate a possible disease recurrence at an early stage. It also provides information about changes in certain cancer-driving genes. This is what scientists from the German Consortium for Translational Cancer Research (DKTK), a partner site at Charité Berlin, have discovered with the help of state-of-the-art molecular biological methods. They believe that this principle can be used in clinical practice as a gentle method for the early detection of recurrent tumors.

In the DKTK, the German Cancer Research Center (DKFZ) in Heidelberg, as the core center, joins forces in the long term with university partner sites in Germany that have a special reputation for oncology.

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Neuroblastomas are malignant tumors that occur predominantly in infants and young children. They arise from cells of the embryonic nervous system and usually form in the spinal chord or the adrenal gland. The course of the disease varies widely. About half of neuroblastomas are particularly aggressive and may recur after therapy. In this case, the patients' chances of survival are very low.

Recurrence is triggered by a small number of tumor cells surviving the therapy. Detecting this so-called minimal residual disease at an early stage - if possible before it can lead to relapses - can improve the further prognosis of the affected children. A prerequisite for this is continuous monitoring with diagnostic methods, because several surgical procedures to remove tissue in series would be far too stressful for those affected. "A promising alternative to tissue analysis is provided by so-called liquid biopsies, which are obtained in a minimally invasive way, for example by taking a sample of the patient's blood or cerebrospinal fluid," explains pediatrician Hedwig Deubzer from the DKTK partner site at the Charité in Berlin. She and her team are researching such methods.

Scientists had already succeeded in detecting cell-free genetic material from tumor cells, so-called ctDNA, in the blood and cerebrospinal fluid of children with neuroblastoma using molecular biological techniques. The DKTK team now investigated whether ctDNA from liquid biopsies could be used as a diagnostic marker to follow the course of the disease - with success. It was able to show that cell-free tumor DNA can be detected early in liquid biopsies from high-risk neuroblastoma patients. "We even identified two patients who had no signs of disease progression up to that point," Deubzer said. "We anticipate that liquid biopsy will be very suitable for routine clinical use because of its sensitivity and the fact that sample material can be easily obtained."

The researchers were also able to show that ctDNA fragments are not only useful as an early warning system for the return of neuroblastoma after therapy. They also provide information about molecular changes in tumor DNA that occur over time and that may be relevant to therapy. The researchers also found such dynamic changes in the region of two known cancer driver genes: the MYCN gene and the ALK gene. "The ALK gene in particular represents a target for cancer therapy with an ALK inhibitor," Deubzer said. "The early detection of alterations in this gene therefore also means a new option for follow-up treatment for some patients."

Marco Lodrini, Josefine Graef, Theresa M. Thole-Kliesch, Kathy Astrahantseff, Annika Sprüssel, Maddalena Grimaldi, Constantin Peitz, Rasmus B. Linke, Jan F. Hollander, Erwin Lankes, Annette Künkele, Lena Oevermann, Georg Schwabe, Joerg Fuchs, Annabell Szymansky, Johannes H. Schulte, Patrick Hundsdoerfer, Cornelia Eckert, Holger Amthauer, Angelika Eggert, Hedwig E. Deubzer
Clin Cancer Res 2022, DOI:

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.


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