Division of Cancer Genome Research

Prof. Dr. Holger Sültmann

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The emergence of tumors is accompanied by genomic, epigenomic, and transcriptomic changes, which impair cellular control mechanisms. The aims of our research are to identify such changes, to characterize their roles in tumor progression and therapy resistance, and to translate them into clinical applications. Our work focuses on prostate, kidney, and lung cancer. As a member of the International Cancer Genome Consortium (ICGC), we sequenced the total RNA of 140 prostate cancer samples. Based on these data, we perform functional analyses of selected noncoding RNAs using in vitro and in vivo models. We also study the effects of the TMPRSS2/ERG gene fusion on the epigenome and differentiation of prostate cancer cells. In our lung cancer-related projects, we investigate the (epi)genomic heterogeneity and phylogenetic relationships between tumor areas. CRISPR/Cas9-based-screens are utilized to find cancer-associated changes and synthetic lethal factors on chromatin, genome, and transcriptome levels. Recently, we established 3D spheroid and co-culture models to analyze molecular factors and signal transduction pathways leading to therapy resistance. To accelerate the clinical translation of our results, we deploy highly sensitive genomics technologies for the quantification of tumor-specific mutations and other biomarkers in blood plasma DNA from cancer patients (liquid biopsy). In these precision medicine approaches, we monitor patient tumor loads to detect treatment resistance and alternative therapy targets with simple blood tests.

Future Outlook
In the future, we will augment our established cooperations to apply liquid biopsy tests for therapy monitoring of cancer patients in controlled clinical studies. Research towards understanding the occurrence and kinetics of mutated DNA in blood plasma will complement these efforts. A mid-term objective is to use plasma DNA sequencing for the early detection of tumors in cancer risk groups. Basic science projects will focus on investigating the consequences of DNA mutations and lncRNA expression on the (epi)genomic profiles of tumor cells. We will increasingly apply 3D spheroid and co-cultures as well as mouse models to validate genes influencing tumor progression and therapy resistance. These activities will be supported by the utilization of single cell analysis technologies.

Contact

Prof. Dr. Holger Sültmann
Cancer Genome Research (B063)
Deutsches Krebsforschungszentrum
und Nationales Centrum für Tumorerkrankungen (NCT)
Im Neuenheimer Feld 460
69120 Heidelberg
Tel: +49 (0)6221 565934

Selected Publications

  • Dietz S. and Sültmann H. et al. (2017). Patient-specific molecular alterations are associated with metastatic clear cell renal cell cancer progressing under tyrosine kinase inhibitor therapy. Oncotarget, doi: 10.18632/oncotarget.18200
  • Ratz L. et al. (2017). Differential effects of TMPRSS2:ERG gene variants on TGF-? signaling and epithelial to mesenchymal transition in prostate cancer cells. Oncotarget, 8(15), 25115-25130
  • Riediger A.L. and Dietz S. et al. (2016). Mutation analysis of circulating plasma DNA to determine response to EGFR tyrosine kinase inhibitor therapy of lung adenocarcinoma patients. Scientific Reports, 6, 33505
  • Gu L. et al. (2015) BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence. Nature Genetics, 47(1), 22-30
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