Page 83 - Molecular features of low-grade developmental brain tumours

DISTINCT DNA METHYLATION PATTERNS IN SEGA IN TSC
Conclusions
Overall, this study shows that the DNA methylation profile of SEGAs is enriched for the immune system, the MAPK pathway and the ECM organization, strengthening the importance of these pathways in SEGA development and suggests that therapeutic intervention on DNA level could be useful. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway. Although the clinical relevance of these subgroups remains uncertain they could potentially reflect tumour progression or response to treatment other than anti-epileptic drugs and deserve further investigation.
Authorship
EA, JM and AM conceived the study and participated in its design and coordination. FJ, WS, WD, RC, IB, WP, VG, TS, JH, MF, KK, SJ, WG, AMB, CC, FG, LG, FS, JP, AM and EA contributed to the collection and selection of tissue samples or clinical data. DJ performed the methylation 450K analysis. AB, JM, DJ and BS performed the bioinformatics. DNA/RNA isolation, immunohistochemistry and evaluation of immunohistochemistry was performed by AB, supported by AM, CM and JA. Analysis of the data was performed by AB, JM and AM. AB, JM, DJ, BS, AS, AM and EA wrote the paper. All authors read and approved the final manuscript.
Acknowledgements
The authors thank all supporters of the TSC brain bank (Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Warsaw, Poland: J. Jaworski, A Tempes; The Service d’ Anatomie Pathologique, CHI de Creteil and Inserm U676, Hospital Robert Debre, Paris, France: H. Adle-Biassette; Department of Pediatrics, Division of Neuropathology and Neurochemistry, Department of Neurology, Department of Neurosurgery, Medical University Vienna, Austria: M. Feucht, T. Scholl, J. Hainfellner, T. Czech; Department of Neurology and Pathology and Molecular Medicine, Charles University, 2nd Faculty of Medicine, Motol University Hospital, Prague, Czech Republic: P. Krsek, J. Zamecnik; Department of Neuropathology, John Radcliffe Hospital, Oxford, UK: C. Kennard; Department of Anatomic Pathology Sciences, Università Sapienza, Rome, Italy: M. Antonelli, F. Giangaspero; Insitute of Neuropathology, Westfälische Wilhelms – Universität Münster, Münster, Germany: W. Paulus, M. Hasselblatt; Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany: R. Coras, I. Blümcke; Bethel Epilepsy Centre, Bielefeld, Germany: T. Polster, C.G. Bien; Laboratory of Neuropathology, Department of Neurology, Hospital de Santa Maria (CHLN), Lisbon, Portugal: J. Pimentel; Department of Human Pathology and Oncology, University of Florence and Division of Neurosurgery, ‘Anna Meyer’ Pediatric Hospital, Florence, Italy: A. M. Buccoliero, F. Giordano; Department of Pathology, Faculty of Medicine, Hacettepe University, Ankara, Turkey: F. Söylemezoğlu). In this regard we would like to acknowledge all personnel involved in sending us the material. Furthermore, the authors would like to thank Dr. Mark Nellist (Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands) and Dr. David J. Kwiatkowski, MD, PhD (Division
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