Group "Neuroblastoma"

Neuroblastomas are a very heterogeneous group of tumors that almost exclusively occur in children. They develop in the first years of life from immature cells of the peripheral nervous system and in some cases regress by themselves. However, they can also grow extremely aggressively and then become life-threatening.

In order to be able to adapt the intensity of the therapy as closely as possible to the individual characteristics of the tumor, our work group "Neuroblastomas", which corresponds to the DKFZ division "Neuroblastoma Genomics" (headed by PD Dr. Frank Westermann), deals with risk assessment by means of molecular markers. Also, our aim is to derive individualized therapeutic approaches in order to provide the patient with the best possible treatment.


Main research aspects

We work on molecular risk stratification and customized therapies for particularly aggressive forms of neuroblastoma. For this we need an accurate understanding of the development, progression and therapy resistance of neuroblastomas. Here, a special role is played by a malfunction of the transcription factor MYCN, which is regularly observed in particularly aggressive tumors. MYCN is involved in almost all aspects of tumor formation: unrestrained proliferation, inhibition of differentiation, adaptation of cellular energy metabolism, vascularization, infiltration / metastasis, and genomic instability.

The specific aim of our work is to identify the causative genetic changes in neuroblastoma and to characterize the divergent clinical progression employing comprehensive molecular genetic characterization (project NB genome / epigenome / transcriptome) of the different neuroblastoma subtypes (e.g. by means of global gene expression, DNA methylation analysis and high-throughput sequencing). The project “NB Enhancer Translocations” deals with the detailed characterization of chromosomal rearrangements in neuroblastoma cells, in which regulative genomic regions (so-called "super-enhancers") translocate into the context of oncogenes and thereby activate them. Here, histone modification analyses (ChIP-seq) and 3D chromatin context analyses (e.g. circular chromatin conformation capturing, 4C) are used. In the “NB Achilles” project, we use functional high-throughput analyses (siRNA / shRNA screening procedures) to systematically detect targetable factors in neuroblastoma cells. We are particularly looking for weak spots associated with specific changes in cancer cells (e.g. MYCN amplification, TERT rearrangements, ATRX deletions, chromosome 1p loss) with one focus being dependencies mediated by these changes. We expect that some of these vulnerabilities could be targets for new cancer medicines. In the project “MYC-NET” we use systems biology approaches to investigate the role of the oncoprotein MYCN in cell cycle, apoptosis, and senescence of cancer cells and normal cells. Another focus of our research group is the identification of genetic risk factors for the expression of chromosomal breaks, which can lead to the development of amplifications and other DNA damage in neuronal tumors (“Fragilome” project).

Team

  • PD Dr. Frank Westermann (Group leader)
  • Dr. Larissa Savelyeva (Senior scientist)
  • Dr. Kai-Oliver Henrich (Senior scientist)
  • Dr. Daniel Dreidax (Post Doc)
  • Dr. Sina Gogolin (Post Doc)
  • Dr. Lena Brückner (Post Doc)
  • Umut Toprak (Bioinformatician)
  • Moritz Gartlgruber (PhD student)
  • Maike Nortmeyer (PhD student)
  • Alica Torkov (PhD student)
  • Mona Friedrich (PhD student)
  • Sabine Hartlieb (PhD student)
  • Marta Parzonka (MD student)
  • Elisa Maria Hess (Bachelor student)
  • Lea Wehrmann (PhD student)
  • Selina Jansky (PhD student)
  • Young-Gyu Park (Technician)

PD Dr. Frank Westermann

Group leader "Neuroblastoma"

Postal address:
German Cancer Research Center
Div. Neuroblastoma Genomics / B087
Im Neuenheimer Feld 280
D- 69120 Heidelberg
Germany

Selected publications

  1. 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.
  2. 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.
  3. 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
  4. Schramm A, Köster J, Assenov Y, Althoff K, Peifer M, Mahlow E, Odersky A, Beisser D, Ernst C, Henssen AG, Stephan H, Schröder C, Heukamp L, Engesser A, Kahlert Y, Theissen J, Hero B, Roels F, Altmüller J, Nürnberg P, Astrahantseff K, Gloeckner C, De Preter K, Plass C, Lee S, Lode HN, Henrich KO, Gartlgruber M, Speleman F, Schmezer P, Westermann F, Rahmann S, Fischer M, Eggert A, Schulte JH. Mutational dynamics between primary and relapse neuroblastomas. Nat Genet. 2015 Aug;47(8):872-7. doi: 10.1038/ng.3349. Epub 2015 Jun 29. PubMed PMID: 26121086.