Epigenomics

 

Principal Investigators

 

Prof. Dr. Stephan Frank

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Dr. Jürgen Hench

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Group Members

 

Dr. Claus Hultschig

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Our Science

Our current research efforts are focused on machine learning-based epigenomic tumor diagnostics. The introduction of a brain tumor DNA methylation classifier (Capper et al., Nature 2018) has prompted efforts to establish a respective diagnostic pipeline in our institute. Employing DNA microarrays, we have so far analyzed DNA methylation profiles of more than 2000 tumor samples in a diagnostic context. However, as this approach is time-consuming, we have more recently begun to establish a nanopore sequencing-based pipeline to enable same-day epigenomic (and genomic) profiling. Its underlying workflow (Euskirchen et al., Acta Neuropathol 2017) is much less equipment- and resource-dependent, and allows molecular tumor typing even before histological sections or special stains become available. In addition, we recently launched an open-source portal for colleagues around the world to compare their methylation datasets with a continuously growing dataset of annotated reference cases (www.epidip.org). Finally, as part of an international consortium, we have contributed (and continue to do so) to a number of collaborative efforts; relevant publications below.

Screenshot of the EpiDiP-Tool.
 

Relevant Publications

  • Janin M, Ortiz-Barahona V, de Moura MC, et al. Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program. Acta Neuropathol. 2019 138(6):1053-1074. doi:10.1007/s00401-019-02062-4.
  • Haefliger S, Tzankov A, Frank S, et al. NUT midline carcinomas and their differentials by a single molecular profiling method: a new promising diagnostic strategy illustrated by a case report. Virch Arch. 2020.
  • Neumann JE, Spohn M, Obrecht D, et al. Molecular characterization of histopathological ependymoma variants. Acta Neuropathol. 2020
  • Yang D, Holsten T, Börnigen D, et al. Ependymoma relapse goes along with a relatively stable epigenome, but a severely altered tumor morphology. Brain Pathol. 2020
  • Sievers P, Schrimpf D, Stichel D, et al. Posterior fossa pilocytic astrocytomas with oligodendroglial features show frequent FGFR1 activation via fusion or mutation. Acta Neuropathol. 2020.
  • Hou Y, Pinheiro J, Sahm F, et al. Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA. Acta Neuropathol. 2019.
  • Capper D, Engel NW, Stichel D, et al. DNA methylation-based reclassification of olfactory neuroblastoma. Acta Neuropathol. 2018.
  • Capper D, Jones DTW, Sill M, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018.
  • Waszak SM, Northcott PA, Buchhalter I, et al. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol. 2018.
  • Hench J, Bihl M, Bratic Hench I, et al. Satisfying your neuro-oncologist: a fast approach to routine molecular glioma diagnostics. Neuro-Oncol. 2018.
  • Sturm D, Orr BA, Toprak UH, et al. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell2016.