Division of Neuroblastoma Genomics

PD Dr. Frank Westermann

Figure 1: Clustering based on enhancer activity as defined by tumor-ChiP-seq.
Figure 2: Translocation event in neuroblastoma cells analyzed using 4C– enhancer hijacking.
© dkfz.de

Neuroblastoma is the most common pediatric single-entity solid cancer derived from primitive cells of the peripheral sympathetic nervous system. It is characterized by heterogeneous clinical phenotypes ranging from spontaneous regression to malignant progression despite intensive multimodal therapies. Malfunction of the MYCN transcription factor is a key feature of neuroblastoma biology and is involved in almost every aspect of tumor formation such as unrestricted proliferation, differentiation inhibition, reprogramming of cellular energetics, angiogenesis, infiltration/metastasis and genomic instability.

Overall aim of our work is to integrate next-generation molecular diagnostics for a more precise patient risk stratification and to develop molecularly targeted therapies based on a better understanding of the molecular mechanisms underlying neuroblastoma tumorigenesis. We use microarray-based technologies as well as next-generation sequencing with the specific aim to define genetic and epigenetic alterations associated with distinct neuroblastoma subtypes (project NB genome/epigenome/transcriptome). The project NB oncogenes activated by enhancer hijacking focuses on the comprehensive characterization of enhancer translocations in NB using an integrated analysis combining whole genome sequencing (WGS), RNA-seq, ChIP-seq and 4C chromatin context analyses. In addition, we use high-throughput si/shRNA screens to disclose neuroblastoma-specific vulnerabilities associated with distinct genetic aberrations, such as amplified MYCN, TERT rearrangements, or ATRX deletions (project NB Achilles). These structural and functional genomic screens are further complemented by systems biology approaches to understand MYCN protein functions regulating cell cycle progression, apoptosis and senescence in normal and cancer cells (project MYC-NET). Finally, we have a focus on the identification of molecular pathways involved in the activation of chromosomal fragile sites as a prominent initiating event in the generation of chromosomal damage, particularly DNA deletions and DNA amplifications (Fragilome Project).


PD Dr. Frank Westermann
Neuroblastoma Genomics (B087)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 423219

Selected Publications

  • Ryl T, Kuchen EE, Bell E, Shao C, Flórez AF, Mönke G, Gogolin S, Friedrich M, Lamprecht F, Westermann F*, Höfer T*. Cell-Cycle Position of Single MYC-Driven Cancer Cells Dictates Their Susceptibility to a Chemotherapeutic Drug. Cell Syst. 2017 Sep 27;5(3):237-250.e8. doi: 10.1016/j.cels.2017.07.005. Epub 2017 Aug 23. PubMed PMID: 28843484.
  • Henrich KO, Bender S, Saadati M, Dreidax D, Gartlgruber M, Shao C, Herrmann C, Wiesenfarth M, Parzonka M, Wehrmann L, Fischer M, Duffy DJ, Bell E, Torkov A, Schmezer P, Plass C, Höfer T, Benner A, Pfister SM, Westermann F. Integrative Genome-Scale Analysis Identifies Epigenetic Mechanisms of Transcriptional Deregulation in Unfavorable Neuroblastomas. Cancer Res. 2016 Sep 15;76(18):5523-37. doi: 10.1158/0008-5472.CAN-15-2507. Epub 2016 Sep 7. PubMed PMID: 27635046.
  • Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, Krämer A, Roncaioli JL, Sand F, Heuckmann JM, Ikram F, Schmidt R, Ackermann S, Engesser A, Kahlert Y, Vogel W, Altmüller J, Nürnberg P, Thierry-Mieg J, Thierry-Mieg D, Mariappan A, Heynck S, Mariotti E, Henrich KO, Gloeckner C, Bosco G, Leuschner I, Schweiger MR, Savelyeva L, Watkins SC, Shao C, Bell E, Höfer T, Achter V, Lang U, Theissen J, Volland R, Saadati M, Eggert A, de Wilde B, Berthold F, Peng Z, Zhao C, Shi L, Ortmann M, Büttner R, Perner S, Hero B, Schramm A, Schulte JH, Herrmann C, O'Sullivan RJ, Westermann F*, Thomas RK*, Fischer M*. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015 Oct 29;526(7575):700-4. doi: 10.1038/nature14980. Epub 2015 Oct 14. PubMed PMID: 26466568; PubMed Central PMCID: PMC4881306
  • Ackermann S, Cartolano M, Hero B, Welte A, Kahlert Y, Roderwieser A, Bartenhagen C, Walter E, Gecht J, Kerschke L, Volland R, Menon R, Heuckmann JM, Gartlgruber M, Hartlieb S, Henrich KO, Okonechnikov K, Altmüller J, Nürnberg P, Lefever S, de Wilde B, Sand F, Ikram F, Rosswog C, Fischer J, Theissen J, Hertwig F, Singhi AD, Simon T, Vogel W, Perner S, Krug B, Schmidt M, Rahmann S, Achter V, Lang U, Vokuhl C, Ortmann M, Büttner R, Eggert A, Speleman F, O'Sullivan RJ, Thomas RK, Berthold F, Vandesompele J, Schramm A*, Westermann F*, Schulte JH*, Peifer M*, Fischer M*. A mechanistic classification of clinical phenotypes in neuroblastoma. Science. 2018 Dec 7;362(6419):1165-1170. doi: 10.1126/science.aat6768. PubMed PMID: 30523111.* equal contribution
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