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Division of Pediatric Neurooncology

Prof. Dr. Stefan Pfister

Intratumoral heterogeneity demonstrated by amplification of distinct oncogenes (red= MYCN, green = GLI2) in different cell populations of a medulloblastoma sample.
Vergrößerte Ansicht Intratumoral heterogeneity demonstrated by amplification of distinct oncogenes (red= MYCN, green = GLI2) in different cell populations of a medulloblastoma sample.

Pediatric Neurooncology currently is a vibrant field of research with countless critical achievements in recent years to understand the molecular biology of childhood brain tumors and translate molecular findings into clinical practice. This is desperately needed from a clinical perspective, since brain tumors have become the number one cause of cancer related mortality of children, at least in part due to the fact that for the far more frequent hematological neoplasms these achievements have been made well before and have already been in clinical use for many years. Our group aims to bridge the gap between generating genomic screening data (microarray-based as well as by next-generation sequencing) and exploiting these data for the sake of our patients. This on the one hand includes the identification, validation and clinical application of prognostic and predictive biomarkers as well as functional characterization of newly identified mutations in different childhood brain tumors including medulloblastoma, ependymoma, pilocytic astrocytoma, and glioblastoma. The other major focus involves the systematic pre-clinical testing of novel drug targets, often in combination with established cytotoxic drugs and/or chemotherapy to treat models (in vitro and in vivo), and ultimately patients, based on the genetic/molecular signature of the individual tumor (“personalized oncology”).

The immense biological heterogeneity of childhood brain tumors between and within tumors, the knowledge of which is a prerequisite for targeted treatment approaches, is still poorly understood and thus currently hindering such approaches on a regular basis in the clinic. To overcome this shortcoming, we will continue to comprehensively understand the entire genetic and epigenetic diversity of childhood brain tumors within and across histopathological entities. A large and continuously growing repertoire of preclinical models will allow us to specifically test biological hypotheses gained from genome-wide primary tumor analyses in vitro and in vivo before they are recommended for use in patients. Another focus will be the analysis of clonality within tumors, their respective metastases, and tumor relapses by ultra-deep next-generation sequencing techniques. This should allow us to appropriately consider the biological importance of subclones present already in the primary tumor that confer tumor dissemination, local tumor re-growth, and therapy resistance. As a third major focus, we have started focusing on the detection of tumor-specific alterations in moodily fluids, such as cerebrospinal fluid, and plasma, which can be exploited for molecular diagnostics, tumor cell clearance (minimal residual disease), detection of molecular drug targets, and primary resistance mechanisms.

Selected Publications

Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DT, Capper D, Sill M, Buchhalter I, Northcott PA, Leis I, Ryzhova M, Koelsche C, Pfaff E, Allen SJ, Balasubramanian G, Worst BC, Pajtler KW, Brabetz S, Johann PD, Sahm F, Reimand J, Mackay A, Carvalho DM, Remke M, Phillips JJ, Perry A, Cowdrey C, Drissi R, Fouladi M, Giangaspero F, ?astowska M, Grajkowska W, Scheurlen W, Pietsch T, Hagel C, Gojo J, Lötsch D, Berger W, Slavc I, Haberler C, Jouvet A, Holm S, Hofer S, Prinz M, Keohane C, Fried I, Mawrin C, Scheie D, Mobley BC, Schniederjan MJ, Santi M, Buccoliero AM, Dahiya S, Kramm CM, von Bueren AO, von Hoff K, Rutkowski S, Herold-Mende C, Frühwald MC, Milde T, Hasselblatt M, Wesseling P, Rößler J, Schüller U, Ebinger M, Schittenhelm J, Frank S, Grobholz R, Vajtai I, Hans V, Schneppenheim R, Zitterbart K, Collins VP, Aronica E, Varlet P, Puget S, Dufour C, Grill J, Figarella-Branger D, Wolter M, Schuhmann MU, Shalaby T, Grotzer M, van Meter T, Monoranu CM, Felsberg J, Reifenberger G, Snuderl M, Forrester LA, Koster J, Versteeg R, Volckmann R, van Sluis P, Wolf S, Mikkelsen T, Gajjar A, Aldape K, Moore AS, Taylor MD, Jones C, Jabado N, Karajannis MA, Eils R, Schlesner M, Lichter P, von Deimling A, Pfister SM, Ellison DW, Korshunov A, Kool M. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell. 2016 Feb 25;164(5):1060-72

Johann PD, Erkek S, Zapatka M, Kerl K, Buchhalter I, Hovestadt V, Jones DT, Sturm D, Hermann C, Segura Wang M, Korshunov A, Rhyzova M, Gröbner S , Brabetz S, Chavez L, Bens S, Gröschel S, Kratochwil F, Wittmann A, Sieber L, Geörg C, Wolf S, Beck K, Oyen F, Capper D, van Sluis P, Volckmann R, Koster J, Versteeg R, von Deimling A, Milde T, Witt O, Kulozik AE, Ebinger M, Shalaby T, Grotzer M, Sumerauer D, Zamecnik J, Mora J, Jabado N, Taylor MD, Huang A, Aronica E, Bertoni A, Radlwimmer B, Pietsch T, Schüller U, Schneppenheim R , Northcott PA, Korbel JO, Siebert R, Frühwald MC, Lichter P, Eils R, Gajjar A, Hasselblatt M, Pfister SM1, Kool M. Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes. Cancer Cell. 2016 Feb 18. pii: S1535-6108(16)30035-6

Lin CY, Erkek S, Tong Y, Yin L, Federation AJ, Zapatka M, Haldipur P, Kawauchi D, Risch T, Warnatz HJ, Worst BC, Ju B, Orr BA, Zeid R, Polaski DR, Segura-Wang M, Waszak SM, Jones DT, Kool M, Hovestadt V, Buchhalter I, Sieber L, Johann P, Chavez L, Gröschel S, Ryzhova M, Korshunov A, Chen W, Chizhikov VV, Millen KJ, Amstislavskiy V, Lehrach H, Yaspo ML, Eils R, Lichter P, Korbel JO2, Pfister SM, Bradner JE, Northcott PA. Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature. 2016 Feb 4; 530(7588):57-62

Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, Wani K, Tatevossian R, Punchihewa C, Johann P, Reimand J, Warnatz HJ, Ryzhova M, Mack S, Ramaswamy V, Capper D, Schweizer L, Sieber L, Wittmann A, Huang Z, van Sluis P, Volckmann R, Koster J, Versteeg R, Fults D, Toledano H, Avigad S, Hoffman LM, Donson AM, Foreman N, Hewer E, Zitterbart K, Gilbert M, Armstrong TS, Gupta N, Allen JC, Karajannis MA, Zagzag D, Hasselblatt M, Kulozik AE, Witt O, Collins VP, von Hoff K, Rutkowski S, Pietsch T, Bader G, Yaspo ML, von Deimling A, Lichter P, Taylor MD, Gilbertson R, Ellison DW, Aldape K, Korshunov A, Kool M, Pfister SM. Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. Cancer Cell. 2015 May 11;27(5):728-43

last update: 16/03/2016 back to top