
Translationale Tumorforschung
Malignant Tumors of Soft Tissue and Bone
More than 70 types of soft tissue neoplasms have been defined by the WHO classification. Morphologically, sarcomas can be subdivided into two major subgroups: tumors with a non-pleomorphic morphology and those with a pleomorphic phenotype. Non-pleomorphic sarcomas more often carry specific molecular aberrations whereas pleomorphic sarcomas frequently display complex karyotypes.
Three major types of genomic alterations occur in sarcomas:
- Reciprocal translocations (~15%)
- Specific mutations (~25%)
- Amplifications (~10%)
While chromosomal translocations lead to the formation of chimeric fusion genes, the resulting fusion proteins function frequently as transcription factors. Specific mutations are often found in genes encoding tyrosine kinases. Amplifications mainly affect genes which encode important modulators in cell cycle control.
Our research projects in the field of soft tissue and bone pathology focus on:
- The diagnostic, prognostic and/or predictive value of specific markers and genomic alterations in malignant tumors of soft tissue and bone
- The translational exploration of signaling pathways in particular subgroups of soft tissue sarcomas aiming at a better understanding of the underlying tumor biology and the definition of novel therapeutic approaches.
Selected research projects:
- Identification of novel therapeutic targets through functional characterization of oncogenic pathways in synovial sarcoma (SySa)
- Functional characterization of transcription factors in the context of activated PI3K/AKT signaling in myxoid liposarcomas (MLS)
- Identification and characterization of molecular targets in sarcoma cell lines as a basis of innovative therapeutic strategies
- Molecular characterization of novel therapeutic targets in Ewing sarcoma
GROUP MEMBERS
Wolfgang Hartmann, Prof. Dr. med.
Deputy director of the Gerhard-Domagk-Institute of Pathology, Principal Investigator
ORCID: 0000-0002-7609-5021
ResearcherID: G-1893-2017
T +49 251 83-58479
F +49 251 83-57559
wolfgang.hartmann(at)ukmuenster(dot)de
Marcel Trautmann, PD Dr.
Research group leader, Principal Investigator
ORCID: 0000-0002-5842-1196
ResearcherID: B-4627-2015
T +49 251 83-57623
F +49 251 83-57559
marcel.trautmann(at)ukmuenster(dot)de
(in alphabetical order)
- Alina Hildebrand, MedK-PhD student (Dr. med.)
- Charlotte Sohlbach, Technical Assistant / Email
- Esther-Pia Jansen, Technical Assistant / Email
- Hanna Wattendorff, DKH / MedK-PhD student (Dr. med.)
- Ilka Isfort, Postdoctoral researcher / Dr. rer. nat. / Email
- Jonas Breuer, MedK-PhD student (Dr. med.)
- Lorena Heinst, PhD student (Dr. rer. nat.) / Email
- Miriam Schulte, MedK-PhD student (Dr. med.)
- Ruth Berthold, PhD student (Dr. rer. nat.) / Email
- Sandra Elges, Dr. med. (Resident) / Email
Selected key publications:
> Hartmann W. (PubMed), Huss S. (PubMed), Trautmann M. (PubMed) Wardelmann E. (PubMed)
Requirement for YAP1 signaling in myxoid liposarcoma.
Trautmann, M., Cheng, YY., Jensen, P., Azoitei, N., Brunner, I., Hüllein, J., Slabicki, M., Isfort, I., Cyra, M., Berthold, R., Wardelmann, E., Huss, S., Altvater, B., Rossig, C., Hafner, S., Simmet, T., Ståhlberg, A., Åman, P., Zenz, T., Lange, U., Kindler, T., Scholl, C., Hartmann, W., and Fröhling, S.
EMBO Molecular Medicine (2019), Published OnlineFirst March 21
DOI 10.15252/emmm.201809889 / PMID: 30898787 / Read more
SS18-SSX-dependent YAP/TAZ signaling in synovial sarcoma. Isfort, I., Cyra, M., Elges, S., Kailayangiri, S., Altvater, B., Rossig, C., Steinestel, K., Grünewald, I., Huss, S., Eßeling, E., Mikesch, JH., Hafner,S., Simmet, T., Wozniak, A., Schöffski, P., Larsson, OL., Wardelmann, E., Trautmann, M. and Hartmann, W.
Clinical Cancer Research (2019), Published OnlineFirst February 27
DOI: 10.1158/1078-0432.CCR-17-3553 / PMID: 30814111 / Read more
Phosphatidylinositol-3-kinase (PI3K)/Akt signaling is functionally essential in myxoid liposarcoma. Trautmann, M., Cyra, M., Isfort, I., Jeiler, B., Krüger, A., Grünewald, I., Steinestel, K., Altvater, B., Rossig, C., Hafner, S., Simmet, T., Becker, J., Åman, P., Wardelmann, E., Huss, S. and Hartmann, W.
Molecular Cancer Therapeutics (2019), Published OnlineFirst February 20
DOI: 10.1158/1535-7163.MCT-18-0763 / PMID: 30787173 / Read more
Activating mutations in the MAP‐kinase pathway define non‐ossifying fibroma of bone. Baumhoer, D., Kovac, M., Sperveslage, J., Ameline, B., Strobl, AC., Krause, A., Trautmann, M., Wardelmann, E., Nathrath, M., Höller, S., Hardes, J., Gosheger, G., Krieg, AH., Vieth, V., Tirabosco, R., Amary, F., Flanagan, AM., and Hartmann, W.
The Journal of Pathology (2018). First published: December 13
DOI: 10.1002/path.5216 / PMID: 30549028 / Read more
FUS-DDIT3 fusion protein driven IGF-IR signaling is a therapeutic target in myxoid liposarcoma. Trautmann, M., Menzel, J., Bertling, C., Cyra, M., Isfort, I., Steinestel, K., Elges, S., Grünewald, I., Altvater, B., Rössig, C., Fröhling, S., Hafner, S., Simmet, T., Åman, P., Wardelmann, E., Huss, S. and Hartmann, W.
Clinical Cancer Research (2017), Published OnlineFirst July 28
DOI: 10.1158/1078-0432.CCR-17-0130 / PMID: 28637688 / Read more
MDM2 and CDK4 amplifications are rare events in salivary duct carcinomas. Grünewald, I., Trautmann, M., Busch, A., Bauer, L., Huss, S., Schweinshaupt, P., Vollbrecht, C., Odenthal, M., Quaas, A., Buttner, R., Meyer, M. F., Beutner, D., Huttenbrink, K. B., Wardelmann, E., Stenner, M., and Hartmann, W.
Oncotarget. 2016;7(46):75261-72
DOI: 10.18632/oncotarget.12127 / PMID: 27662657 / Read more
Deep sequencing in conjunction with expression and functional analyses reveals activation of FGFR1 in ewing sarcoma. Agelopoulos, K., Richter, G. H., Schmidt, E., Dirksen, U., von Heyking, K., Moser, B., Klein, H. U., Kontny, U., Dugas, M., Poos, K., Korsching, E., Buch, T., Weckesser, M., Schulze, I., Besoke, R., Witten, A., Stoll, M., Kohler, G., Hartmann, W., Wardelmann, E., Rossig, C., Baumhoer, D., Jurgens, H., Burdach, S., Berdel, W. E., and Muller-Tidow, C.
Clinical Cancer Research, 2015. 21(21):4935-46
DOI: 10.1158/1078-0432.CCR-14-2744 / PMID: 26179511 / Read more
SRC inhibition represents a potential therapeutic strategy in liposarcoma. Sievers, E., Trautmann, M., Kindler, D., Huss, S., Gruenewald, I., Dirksen, U., Renner, M., Mechtersheimer, G., Pedeutour, F., Aman, P., Nishio, J., Schildhaus, H. U., Kirfel, J., Schirmacher, P., Wardelmann, E., Buettner, R., and Hartmann, W.
International Journal of Cancer. 2015;137(11):2578-88
DOI: 10.1002/ijc.29645 / PMID: 26084847 / Read more
SS18-SSX fusion protein-induced Wnt/beta-catenin signaling is a therapeutic target in synovial sarcoma. Trautmann, M., Sievers, E., Aretz, S., Kindler, D., Michels, S., Friedrichs, N., Renner, M., Kirfel, J., Steiner, S., Huss, S., Koch, A., Penzel, R., Larsson, O., Kawai, A., Tanaka, S., Sonobe, H., Waha, A., Schirmacher, P., Mechtersheimer, G., Wardelmann, E., Buttner, R., and Hartmann, W.
Oncogene. 2014;33(42):5006-16
DOI: 10.1038/onc.2013.443 / PMID: 24166495 / Read more
SRC signaling is crucial in the growth of synovial sarcoma cells. Michels, S., Trautmann, M., Sievers, E., Kindler, D., Huss, S., Renner, M., Friedrichs, N., Kirfel, J., Steiner, S., Endl, E., Wurst, P., Heukamp, L., Penzel, R., Larsson, O., Kawai, A., Tanaka, S., Sonobe, H., Schirmacher, P., Mechtersheimer, G., Wardelmann, E., Buttner, R., and Hartmann, W.
Cancer Research. 2013;73(8):2518-28
DOI: 10.1158/0008-5472.CAN-12-3023 / PMID: 23580575 / Read more
Phosphatidylinositol-3'-kinase/AKT signaling is essential in synovial sarcoma. Friedrichs, N., Trautmann, M., Endl, E., Sievers, E., Kindler, D., Wurst, P., Czerwitzki, J., Steiner, S., Renner, M., Penzel, R., Koch, A., Larsson, O., Tanaka, S., Kawai, A., Schirmacher, P., Mechtersheimer, G., Wardelmann, E., Buettner, R., and Hartmann, W.
International Journal of Cancer. 2011;129(7):1564-75
DOI: 10.1002/ijc.25829 / PMID: 21128248 / Read more
Activation of phosphatidylinositol-3'-kinase/AKT signaling is essential in hepatoblastoma survival. Hartmann, W., Kuchler, J., Koch, A., Friedrichs, N., Waha, A., Endl, E., Czerwitzki, J., Metzger, D., Steiner, S., Wurst, P., Leuschner, I., von Schweinitz, D., Buettner, R., and Pietsch, T.
Clinical Cancer Research, 2009. 15(14):4538-45
DOI: 10.1158/1078-0432.CCR-08-2878 / PMID: 19584164 / Read more
Insulin-like growth factor-1 receptor acts as a growth regulator in synovial sarcoma. Friedrichs, N., Kuchler, J., Endl, E., Koch, A., Czerwitzki, J., Wurst, P., Metzger, D., Schulte, J. H., Holst, M. I., Heukamp, L. C., Larsson, O., Tanaka, S., Kawai, A., Wardelmann, E., Buettner, R., Pietsch, T., and Hartmann, W.
The Journal of Pathology, 2008. 216(4):428-39
DOI: 10.1002/path.2438 / PMID: 18855347 / Read more
Phosphatidylinositol 3'-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN. Hartmann, W., Digon-Sontgerath, B., Koch, A., Waha, A., Endl, E., Dani, I., Denkhaus, D., Goodyer, C. G., Sorensen, N., Wiestler, O. D., and Pietsch, T.
Clinical Cancer Research, 2006. 12(10):3019-27
DOI: 10.1158/1078-0432.CCR-05-2187 / PMID: 16707597 / Read more
Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells. Hartmann, W., Koch, A., Brune, H., Waha, A., Schuller, U., Dani, I., Denkhaus, D., Langmann, W., Bode, U., Wiestler, O. D., Schilling, K., and Pietsch, T.
American Journal of Pathology, 2005. 166(4):1153-62
DOI: 10.1016/S0002-9440(10)62335-8 / PMID:15793295 / Read more
Selected research funding:
in alphabetical order:
- BONFOR
- Deutsche Forschungsgemeinschaft (DFG)
- Deutsche Krebshilfe
- Dr. Eberhard und Hilde Rüdiger Stiftung
- GlaxoSmithKline Stiftung
- Innovative Medical Research (IMF) - Medical Faculty of the Universität Münster
- MedK - Medical Faculty of the Universität Münster
- Wilhelm Sander-Stiftung
CONTACT
GDI - CANCER RESEARCH LAB
T (Lab):
+49 251 83-57626 or -58464
T (Office):
+49 251 83-55444 or -58461
F +49 251 83-57559
Visiting address (Google maps):
Domagkstr. 17
48149 Münster, Germany
Our cancer research lab is located at the Gerhard-Domagk-Institute of Pathology / University Hospital Münster (UKM), Germany


