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Prostate Cancer Genomics and Transcriptomics

Functional analysis of coding and noncoding RNA in prostate cancer

In the framework of the ICGC project "The Genomes of Early Onset Prostate Cancers", we sequenced the transcriptomes (mRNA and miRNA). To increase our understanding of processes contributing to prostate cancer progression, we have analyzed selected RNAs from these signatures using cellular assays and RNA interference methodologies.

Selected Publications
:

  • Bauer S, Ratz L, Heckmann-Nötzel D, Kaczorowski A, Hohenfellner M, Altevogt P, Kristiansen G, Duensing S, Klauck SM, Sültmann H. miR-449a repression leads to activated NOTCH signaling in TMPRSS2:ERG fusion positive prostate cancer cells. Cancers 13(5), 964, 2021
  • Angeles AK, Heckmann D, Flosdorf N, Duensing S, Sültmann H. The ERG-regulated LINC00920 promotes prostate cancer cell survival via the 14-3-3ε- FOXO pathway. Molecular Cancer Research 18(10):1545-1559, 2020
  • The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. Pan-cancer analysis of whole genomes. Nature 578(7793), 82-93, 2020
  • Gerhauser C, Favero F, Risch T, Simon R, Feuerbach L, Assenov Y, Heckmann D, (...), Sültmann H, Brors B, Plass C, Yaspo ML, Korbel JO, Schlomm T, Weischenfeldt J. Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories. Cancer Cell 34(6):996-1011, 2018
  • 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

Cooperations: Depts. of Urology and Molecular Urooncology at Heidelberg University Medical Center; Div. of Biostatistics, DKFZ

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

© dkfz.de

Lung cancer is the main cause of mortality among all malignancies in western countries. The prognosis of the disease is very poor. 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 (Liquid biopsy) to monitor tumor progression and therapy.

Selected Publications:

  • Angeles AK*, Christopoulos P*, Yuan Z, Bauer S, Janke F, Ogrodnik SJ, Reck M, Schlesner M, Meister M, Schneider MA, Dietz S, Stenzinger A, Thomas M, Sültmann H. Early identification of disease progression in ALK-rearranged lung cancer using circulating tumor DNA analysis.
    NPJ Precision Oncology, 5(1):100, 2021
  • Dietz S, Christopoulos P, Yuan Z, Gu L, Volckmar A-L, Ogrodnik SJ, Angeles AK, Dalle Fratte C, Zemojtel T, Schneider MA, Kazdal D, Endris V, Meister M, Muley T, Cecchin E, Reck M, Schlesner M, Thomas M, Stenzinger A, Sültmann H. Longitudinal therapy monitoring of ALK-positive non-small cell lung cancer by copy number profiling combined with targeted sequencing of cell-free DNA. EBioMedicine 62:103103, 2020
  • Dietz S, Lifshitz A, Kazdal D, Harms A, Endris V, Winter H, Stenzinger A, Warth A, Sill M, Tanay A, Sültmann H. Global DNA methylation reflects spatial heterogeneity and molecular evolution of lung adenocarcinomas. Int J Cancer 144(5):1061-1072, 2019
  • 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. Sci Rep 6:33505, 2016

Cooperations: Thoraxklinik Heidelberg; Dept. of Pathology at Heidelberg University Medical Center

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

Genomics of Diseases

© dkfz.de

Our genomics expertise is utilized in cooperative projects aiming at the analysis of genes and biological processes in diverse diseases. For example, we have contributed to the characterization of spatial and molecular heterogeneity of renal cell cancers, to the investigation of viral sequences in cancer genomes, and to the identification of the receptor for Hepatitis B viruses entering mammalian cells.

Selected Publications:

  • Zapatka M, Borozan I, Brewer, DS, Iskar M, Grundhoff A, Alawi M, Desai N, Sültmann H, Moch H, PCAWG Pathogens Working Group, ICGC/TCGA Pan-cancer Analysis of Whole Genomes Network, Cooper CS, Eils R, Ferretti V, Lichter P. The landscape of viral associations in human cancer. Nature Genetics 52(3):320-330, 2020
  • Christopoulos P#, Dietz S#, Kirchner M, Volckmar AL, Endris V, Neumann O, Ogrodnik S, Heussel CP, Herth FJ, Eichhorn M, Meister M, Budczies J, Allgäuer M, Leichsenring J, Zemojtel T, Bischoff H, Schirmacher P, Thomas M, Sültmann H*, Stenzinger A*. Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival. Cancers, 11, 124, 2019
  • Zhang Z, Filzmayer C, Ni Y, Sültmann H, Mutz P, Hiet M-S, Vondran FWR, Bartenschlager R, Urban S. Hepatitis D Virus replication is sensed by MDA5 and induces IFN-β/λ responses in hepatocytes. J Hepatol 69(1):25-35, 2018
  • 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. Nat Commun 7:ncomms11845, 2016

Cooperations: Depts. of Urology and Molecular Urooncology at Heidelberg University Medical Center; Div. of Molecular Genetics, DKFZ Heidelberg; Hepatitis B Research Group, Heidelberg University

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

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