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

  • Patel A, Dogan H, Payne A, et al. Rapid-CNS2: rapid comprehensive adaptive nanopore-sequencing of CNS tumors, a proof-of-concept study. Acta Neuropathol. 2022 Mar 31.
  • Hench J, Vlajnic T, Soysal SD, et al. An Integrated Epigenomic and Genomic View on Phyllodes and Phyllodes-like Breast Tumors. Cancers (Basel). 2022 Jan 28;14(3):667.
  • Bockmayr M, Harnisch K, Pohl LC, et al. Comprehensive profiling of myxopapillary ependymomas identifies a distinct molecular subtype with relapsing disease. Neuro Oncol. 2022 Apr 5:noac088.
  • Borlin PR, Brazzola P, Frontzek K, et al. Cancer in children with biallelic BRCA1 variants and Fanconi anemia-like features: Report of a malignant brain tumor in a young child. Pediatr Blood Cancer. 2022 Apr 4:e29680.
  • Maas SLN, Stichel D, Hielscher T, et al.; German Consortium on Aggressive Meningiomas (KAM). Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated. J Clin Oncol. 2021 Oct 7:JCO2100784.
  • Della Monica R, Cuomo M, Visconti R, et al. Evaluation of MGMT gene methylation in neuroendocrine neoplasms. Oncol Res. 2021 May 20
  • Suwala AK, Stichel D, Schrimpf D, et al. Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1. Acta Neuropathol. 2021 Jul;142(1):179-189.
  • Glöss S, Jurmeister P, Thieme A, et al. IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome. Am J Surg Pathol. 2021 Sep 1;45(9):1190-1204.
  • Hench IB, Monica RD, Chiariotti L, et al. Fast routine assessment of MGMT promoter methylation. Neurooncol Adv. 2020 Dec 5;3(1):vdaa170.
  • Koelsche C, Schrimpf D, Stichel D, et al. Sarcoma classification by DNA methylation profiling. Nat Commun. 2021 Jan 21;12(1):498. doi: 10.1038/s41467-020-20603-4.
  • Zschernack V, Jünger ST, Mynarek M, et al. Supratentorial ependymoma in childhood: more than just RELA or YAP. Acta Neuropathol. 2021 Jan 22. doi: 10.1007/s00401-020-02260-5.
  • Sievers P, Sill M, Blume C, et al. Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1. Acta Neuropathol. 2020 Dec 14. doi: 10.1007/s00401-020-02247-2. 
  • Sievers P, Sill M, Schrimpf D, Stichel D, et al. A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile, H3K27me3 loss and frequent alteration of EGFR. Neuro Oncol. 2020 Nov 1:noaa251.
  • 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.