Researchers at the German Cancer Research Center (DKFZ) and the National Center for Tumor Diseases (NCT) Heidelberg have elucidated the molecular genetic background of a newly discovered sarcoma subtype that occurs in children and adults. The findings have led to several potential therapeutic approaches that could be tested clinically in the future.
The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center (DKFZ) and Heidelberg University Hospital (UKHD).
Soft-tissue sarcomas are malignant tumors of the connective tissue. They are rare and characterized by histologic diversity and a variable clinical course, ranging from slow-growing to very aggressive and metastatic. Soft-tissue sarcomas also include the group of rhabdomyosarcomas, which originate from skeletal muscle cells. Researchers at DKFZ and NCT Heidelberg have investigated a recently discovered rhabdomyosarcoma subtype characterized by fusions of the TFCP2 gene with various partner genes.
Rhabdomyosarcomas with TFCP2 fusions occur primarily in the head and neck region and are very aggressive and usually fatal as they do not respond to standard therapies. Until now, their molecular origin was largely unknown. Claudia Scholl, Head of the Division of Applied Functional Genomics at DKFZ and NCT Heidelberg, explains: “Through our very detailed functional and mechanistic studies in the laboratory, we were able to elucidate the development of this disease and thus find weak points in the tumor cells that might be exploited therapeutically.”
The motivation to study TFCP2 sarcomas in the laboratory resulted from the DKFZ/NCT/DKTK MASTER precision oncology program, in which these tumors, which were still unknown at the time, had been observed several times. In addition, the researchers integrated patients from the INFORM program, which – in a similar approach to MASTER – focuses on children with advanced and difficult-to-treat cancers. This resulted in a joint, highly collaborative endeavor across scientific and clinical disciplines.
Through the molecular analysis of patient tumors and detailed laboratory tests, the researchers were able to show that tumors with TFCP2 fusions likely represent a separate sarcoma subtype that should not be classified as rhabdomyosarcoma. In addition, several potential approaches were identified for the targeted treatment of this aggressive disease.
Stefan Fröhling, Managing Director at NCT Heidelberg and Head of the Division of Translational Medical Oncology at DKFZ, emphasizes: “The study provides important results and is a prime example of the entire translational cancer research cycle. Clinically anchored analyses in MASTER and INFORM have led to in-depth investigations in the laboratory. The new therapeutic targets discovered there will be fed back into the clinic and hopefully improve the treatment of a patient group whose disease has been underresearched and remains an unmet medical need.”
MASTER: Molecularly Aided Stratification for Tumor Eradication Research
INFORM: INdividualized Therapy FOr Relapsed Malignancies in Childhood
Publication:
Julia Schöpf, Sebastian Uhrig, Christoph E. Heilig, Kwang-Seok Lee, Tatjana Walther, Alexander Carazzato, Anna Maria Dobberkau, Dieter Weichenhan, Christoph Plass, Mark Hartmann, Gaurav D. Diwan, Zunamys Carrero, Claudia R. Ball, Tobias Hohl, Thomas Kindler, Patricia Rudolph-Hähnel, Dominic Helm, Martin Schneider, Anna Nilsson, Ingrid Øra, Roland Imle, Ana Banito, Robert B. Russell, Barbara C. Jones, Daniel B. Lipka, Hanno Glimm, Daniel Hübschmann, Wolfgang Hartmann, Stefan Fröhling, Claudia Scholl: Multi-Omic and Functional Analysis for Classification and Therapeutic Targeting of Sarcomas with FUS-TFCP2 or EWSR1-TFCP2 Fusions; Nature Communications, doi: 10.1038/s41467-023-44360-2
An image of the press release is available free of charge on the internet at:
Image information: Immunofluorescence microscopy image of muscle progenitor cells whose maturation is blocked by a TFCP2 fusion.
Note on the use of images for press releases
Use is free of charge. The NCT Heidelberg permits one-time use in connection with reporting on the subject of the press release. Please quote the copyright "Caroline Adomeit" as photo credit. The image material may only be passed on to third parties after prior consultation with NCT Communications (Phone: +49 6221 42-1755, e-mail: martin.staiger@nct-heidelberg.de). Use for commercial purposes is prohibited.
Press contact:
Dr. Martin Staiger
Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
Kommunikation und Veranstaltungen
Im Neuenheimer Feld 460
69120 Heidelberg
Tel.: +49 6221 42-1755
E-Mail: martin.staiger@nct-heidelberg.de
www.nct-heidelberg.de
Dr. Sibylle Kohlstädt
Deutsches Krebsforschungszentrum (DKFZ)
Strategische Kommunikation und Öffentlichkeitsarbeit
Im Neuenheimer Feld 280
69120 Heidelberg
Tel.: +49 6221 42-2843
Fax: +49 6221 42-2968
E-Mail: s.kohlstaedt@dkfz.de
www.dkfz.de
Dr. Stefanie Seltmann
Universitätsklinikum Heidelberg und Medizinische Fakultät der Universität Heidelberg
Presse- und Öffentlichkeitsarbeit
Im Neuenheimer Feld 672
69120 Heidelberg
Tel.: +49 6221 56-5052
Fax: +49 6221 56-4544
E-Mail: stefanie.seltmann@med.uni-heidelberg.de
www.klinikum.uni-heidelberg.de
The National Center for Tumor Diseases (NCT) Heidelberg
The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center, Heidelberg University Hospital and German Cancer Aid. The NCT's goal is to link promising approaches from cancer research with patient care from diagnosis to treatment, aftercare and prevention. The interdisciplinary tumor outpatient clinic is the central element of the NCT. Here the patients benefit from an individual treatment plan prepared in a timely manner in interdisciplinary expert rounds, the so-called tumor boards. Participation in clinical studies provides access to innovative therapies. The NCT thereby acts as a pioneering platform that translates novel research results from the laboratory into clinical practice. The NCT cooperates with self-help groups and supports them in their work. The pediatric oncologists at the KiTZ work together in joint structures with the NCT Heidelberg.
German Cancer Research Center (DKFZ)
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also 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 questions relating to cancer.
To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:
- National Center for Tumor Diseases (NCT, 6 sites)
- German Cancer Consortium (DKTK, 8 sites)
- Hopp Children's Cancer Center (KiTZ) Heidelberg
- Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
- DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
- National Cancer Prevention Center (jointly with German Cancer Aid)
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.
Heidelberg University Hospital and Faculty of Medicine: Internationally Renowned Patient Care, Research and Teaching
Heidelberg University Hospital (Universitätsklinikum Heidelberg, UKHD) is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University (Medizinische Fakultät Heidelberg, MFHD) belongs to the internationally renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. Heidelberg University Hospital and the Medical Faculty of Heidelberg University employs around 14.500 employees and is committed to providing trainings and qualifications. Every year, around 86,000 patients and more than 1.100.000 outpatient cases are treated in more than 50 clinical departments with almost 2.500 beds. Together with the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the German Cancer Aid, the UKHD established the first National Center for Tumor Diseases (NCT) in Heidelberg. The goal is to provide care at the highest level as an oncology center of excellence and to rapidly transfer promising approaches from cancer research to the hospital. In addition, the UKHD operates in partnership with the DKFZ and the University of Heidelberg the Hopp Children’s Cancer center Heidelberg (KiTZ), a unique and nationally known therapy and research center for oncological and hematological diseases in children and adolescents. The Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany. Currently, there are about 4.000 future physicians studying in Heidelberg.