Prostate Cancer Genome Research

Prostate Cancer Genome and transcriptome sequencing

Prostate cancer (PCA) is generally considered a tumor of elderly men. However, a small fraction of prostate cancers are diagnosed at the age of 50 years or less. A better understanding of these tumors is particularly relevant as finding optimal treatment regimens is most critical in young cancer patients. In the framework of the ICGC-consortium "The Genomes of Early Onset Prostate Cancers", the genomes and epigenomes of 240 PCA of young men (≤ 50y) were characterized. We sequenced the transcriptomes of 140 mRNA and miRNA samples from these patients.


  • Gu L, Frommel S, Oakes CC, Simon R, Grupp K, Gerig C, Bär D, Robinson M, Baer C, Weiss M, Gu Z, Kuner R, Sültmann H, Borsig L, Yaspo ML, Brors B, Korbel J, Schlomm T, Sauter G, Eils R, Plass C, Santoro R. TIP5/BAZ2A Links Polycomb Repression and Epigenetic Remodelling with Recurrence in Prostate Cancer. Nature Genetics 47:22-33, 2015
  • Weischenfeldt J, Simon, R, Feuerbach L, Schlangen K, Weichenhan D, Minner S, Wuttig D, Warnatz H-J, Stehr H, Rausch T, Jäger N, Gu L, Bogatyrova O, Claus R, Eils J, Eils R, Gerhäuser C, Huang P-H, Hutter B, Kabbe R, Lawerenz C, Radomski S, Bartholomä C, Fälth M, Gade S, Schmidt M, von Kalle C, Benes V, Stütz AM, Zichner T, Mader M, Amstislavskiy V, Avci M, Lehrach H, Parkhomchuk A, Sultan M, Burkhardt L, Gräfen M, Huland H, Kluth M, Krohn A, Sirma H, Stumm L, Sültmann H, Sauter G, Plass C, Brors B, Yaspo ML, Korbel JO, Schlomm T. Integrative genomic analyses reveal androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell 23(2):159-170, 2013

Cooperations: Div. of Theoretical Bioinformatics and Translational Oncology, DKFZ; Max-Planck-Institute for Molecular Genetics, Berlin

Support: German Federal Ministry for Education and Research (BMBF) in the program for medical genome research, International Cancer Genome Consortium (ICGC).

Functional analysis of coding and noncoding RNA in prostate cancer

These projects aim at the generation and integration of orthogonal molecular data in order to increase our understanding of processes contributing to prostate cancer progression. Selected genes from these signatures are characterized in cellular assays using cell lines and RNA interference methodologies.

Selected Publications

  • Ratz L, Laible M, Kacprzyk LA, Wittig-Blaich SM, Tolstov Y, Duensing S, Altevogt P, Klauck SM, Sültmann H. TMPRSS2:ERG gene fusion variants induce TGF-ß signaling and epithelial to mesenchymal transition in human prostate cancer cells. Oncotarget 8(15):25115-25130, 2017
  • Pickl JMA, Tichy D, Kuryshev VY, Tolstov Y, Falkenstein M, Schüler J, Reidenbach D, Hotz-Wagenblatt A, Kristiansen G, Roth W, Hadaschik B, Hohenfellner M, Duensing S, Heckmann D, Sültmann H. Ago-RIP-Seq identifies Polycomb repressive complex I member CBX7 as a major target of miR-375 in prostate cancer progression. Oncotarget 7(37):59589-59603, 2016
  • Castelo-Branco P, Leão R, Limpan T, Campbell B, Price A, Zhang C, Börno S, Gomes A, Domingos C, Apolonio JD, Coelho H, Bristow RG, Schweiger MR, Hamilton R, Zlotta A, Figueiredo A, Klocker H, Sültmann H, Tabori U. A cancer specific hypermethylation signature of the TERT promoter predicts biochemical relapse in prostate cancer. A retrospective cohort study. Oncotarget 7(36):57726-57736, 2016
  • Börno ST, Fischer A, Kerick M, Fälth M, Laible M, Brase JC, Kuner R, Dahl A, Grimm C, Isau M, Roehr C, Wunderlich A, Timmermann B, Claus R, Plass C, Graefen M, Simon R, Demichelis F, Rubin MA, Sauter G, Schlomm T, Sültmann H, Lehrach H, Schweiger MR. Increase in genome-wide differential DNA methylation events in TMPRSS2:ERG fusion negative prostate cancers  miRNA-26a hypermethylation. Cancer Discovery 2(11):1024-1035, 2012
  • Brase JC, Johannes M, Schlomm T, Fälth M, Haese A, Steuber T, Beissbarth T, Kuner R, Sültmann H. Circulating miRNA-375 is correlated with tumor progression in prostate cancer. Int. J. Cancer 128(3):608-616, 2011

Cooperations: Depts. of Urology and Molecular Urooncology at Heidelberg University Medical Center; Div. of Urology and Uropathology, Innsbruck Medical University; Div. of Biostatistics, DKFZ; Inst. of Pathology, University Medicine Mainz; Div. of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Berlin

Support: German Federal Ministry for Education and Research (BMBF) in the program for medical genome research (NGFNplus); Institute for Medical Genome Research and Systems Biology, (IMGuS), Vienna, Austria; Austrian National Foundation; Austria Wirtschaftsservice GmbH.

Translational Genomics of Lung Cancer


Lung cancer is the main cause of mortality among all malignancies in western countries. The prognosis of the disease is very poor. Only 12-15% of the patients survive more than 5 years after initial diagnosis of tumors in late stage (III-IV), when often metastases are already manifest. Thus, better diagnostic tools and more efficient and specific therapies are urgently required.

We are analyzing the roles of genes and miRNAs in therapy resistance and perform mutation typing and Panel/exome sequencing of plasma DNA to monitor tumor progression and therapy.

Selected Publications:

  • Dietz S, Harms A, Endris V, Eichhorn F, Kriegsmann M, Longuespée R, Stenzinger A, Sültmann H, Warth A, Kazdal D. Spatial distribution of EGFR and KRAS mutation frequencies correlates with histological growth patterns of lung adenocarcinomas. Int J Cancer 141(9):1841-1848, 2017
  • Riediger AL, Dietz S, Schirmer U, Meister M, Heinzmann-Groth I, Schneider M, Muley T, Thomas M, Sültmann H. Mutation analysis of circulating plasma DNA to determine response to EGFR tyrosine kinase inhibitor therapy of lung adenocarcinoma patients. Scientific Reports 6:33505, 2016
  • Dietz S, Schirmer U, Mercé C, Kuryshev V, von Bubnoff N, Dahl E, Meister M, Muley T, Thomas M, Sültmann H. Low input whole-exome sequencing to determine the representation of the tumor exome in circulating DNA of non-small cell lung cancer patients. PLOS ONE 11(8):e0161012, 2016
  • Hülsmann H, Rolff J, Bender C, Jarahian M, Korf U, Herwig R, Fröhlich H, Thomas M, Merk J, Sültmann H, Kuner R. Activation of AMP-activated protein kinase (AMPK) sensitizes lung cancer cells and H1299 xenografts to Erlotinib. Lung Cancer 86(2):151-157, 2014
  • Kaduthanam S, Gade S, Meister M, Brase JC, Johannes M, Dienemann H, Warth A, Schnabel PA, Herth FJ, Sültmann H, Muley T, Kuner R. Serum miR-142-3p is associated with early relapse in operable lung adenocarcinoma patients. Lung Cancer S0169-5002(13):23-28, 2013

Cooperations: Thoraxklinik Heidelberg; Div. of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Berlin; Dept. of Pathology at Heidelberg University Medical Center; EPO GmbH, Berlin-Buch

Support: German Federal Minstry for Education and Research (BMBF) in the funding programs German Centers for Lung Research (DZL), Medical Systems Biology (PREDICT), and eBio (EPITREAT).

Disease Genomics


We also apply our genomics expertise to cooperative projects aiming at the analysis of genes and biological processes in diverse disease backgrounds. Here, we have contributed to the characterization of spatial and molecular heterogeneity of renal cell cancers, to the molecular analysis of exosome contents in mouse models and to the identification of the receptor for Hepatitis B viruses entering mammalian cells.

Selected Publications:

  • Dietz S, Sültmann H, Du Y, Reisinger E, Riediger AL, Volckmar AL, Stenzinger A, Schlesner M, Jäger D, Hohenfellner M, Duensing S, Grüllich C, Pahernik S. Patient-specific molecular alterations are associated with metastatic clear cell renal cell cancer progressing under tyrosine kinase inhibitor therapy. Oncotarget 8(43):74049-74057, 2017
  • Hoefflin R, Lahrmann B, Warsow G, Hübschmann D, Spath C, Walter B, Chen X, Hofer L, Macher-Goeppinger S, Tolstov Y, Korzeniewski N, Duensing A, Grüllich C, Jäger D, Perner S, Schönberg G, Nyarangi-Dix J, Isaac S, Hatiboglu G, Teber D, Hadaschik B, Pahernik S, Roth W, Eils R, Schlesner M, Sültmann H, Hohenfellner M, Grabe N, Duensing S. Spatial niche formation but not malignant progression is a driving force for intratumoral heterogeneity. Nature Communications 7:11845, 2016
  • Ridder K, Sevko A, Heide J, Dams M, Rupp A, Macas J, Starmann J, Tjwa M, Plate K, Sültmann H, Altevogt P, Umansky P, Momma S. Myeloid derived suppressor cells are the principal target for tumor-derived microvesicles in vivo. OncoImmunology 4(6):e1008371, 2015
  • Honegger A, Schilling D, Bastian S, Sültmann H, Hoppe-Seyler K, Hoppe-Seyler F. The Effects of the HPV E6/E7 Oncogenes on the Intracellular and Exosomal miRNA Compositions of HPV-positive Tumor Cells. PLOS Pathogens 11(3):e1004712, 2015
  • Ni Y, Lempp FA, Mehrle S, Nkongolo S, Kaufman C, Fälth M, Stindt J, Kubitz R, Sültmann H, Urban S. Hepatitis B virus exploits sodium taurocholate co-transporting polypeptide (NTCP) for entering hepatocytes in a species-specific manner. Gastroenterology 146:1070-1083, 2014

Cooperations: Depts. of Urology and Molecular Urooncology at Heidelberg University Medical Center; Institute for Neurology (Edinger Institute), Frankfurt; Hepatitis B Research Group, Heidelberg University, Div. Molecular Therapy of Virus-Associated Tumors, DKFZ

Support: DKFZ intramural funding; German Federal Ministry for Education and Research (BMBF) in the German Cancer Consortium (DKTK).

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