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Division of Pediatric Glioma Research

Dr. David T.W. Jones

Approximation of the frequencies of different histological groupings of pediatric low-grade glioma and associated molecular genetic alterations, split by location within the brain. Adapted from Sturm D, Pfister SM and Jones DTW, J Clin Oncol 2017.
© dkfz.de

Gliomas are the most common form of brain tumor found in children, in total accounting for about half of all central nervous system tumors in 0-19 year olds. Two major categories are usually distinguished: low-grade and high-grade glioma.

Low-grade gliomas are a histologically and biologically varied collection of tumor entities, which are often defined by genetic alterations in the mitogen-activated protein kinase (MAPK) pathway and are typically considered as benign tumors due to their good overall survival rates. This survival, however, often comes at a significant cost to quality of life due to effects of treatment as well as the tumor itself. Multiple recurrences over several years are also not uncommon, creating a heavy burden on patients and their families. Our research aims to learn more about the background of these tumors and their unusual growth behaviour, as well as to identify treatments that are more tailored to individual tumor biology and therefore hopefully have fewer side effects.

High-grade gliomas, in contrast, carry an extremely dismal prognosis. These highly aggressive tumors, most commonly glioblastoma or diffuse intrinsic pontine glioma (DIPG), typically display a much greater degree of genomic instability than lower-grade lesions. Combined disruption of multiple cellular processes leads to rapidly dividing cancer cells that diffusely infiltrate the surrounding normal brain tissue, with an almost universally fatal outcome. Our research in this area aims at understanding the heterogeneity both within single tumors and between individuals, to identify the most important patterns of alterations in the cellular machinery. We then try to recapitulate these changes in model systems, in order to understand their contribution to a cell becoming cancerous and also to test new therapies in a rationally targeted manner.

All of the work being conducted in the lab is based on the application of cutting-edge genomic (next-generation DNA/RNA sequencing), epigenomic (DNA methylation, ChIPseq), and functional technologies (CRISPR/Cas9, somatic gene transfer models) to enhance our understanding of the biological underpinnings of pediatric brain tumors. A further important focus of the group is the translation of this research into practical applications for the benefit of patients. To this end, we are closely involved in the coordination of two international molecular diagnostic programs: the INFORM study for identification of possible drug targets in high-risk pediatric cancers; and the MNP2 study to investigate the value of molecular analysis as a tool for accurate classification of brain tumors.

More information on the Pediatric Neurooncology community in Heidelberg can be found here.

Contact

Dr. David T.W. Jones
Pediatric Glioma Research (B360)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 424675

Selected Publications

  • Sturm D, Andreiuolo F, Gessi M, Kölsche C, Reinhardt A, Sievers P, Wefers AK, Ebrahimi A, Suwala AK, Gielen GH, Sill M, Schrimpf D, Stichel D, Hovestadt V, Daenekas B, Rode A, Hamelmann S, Previti C, Jäger N, Buchhalter, Blattner-Johnson M, Jones BC, Warmuth-Metz M, Bison B, Grund K, Sutter C, Hirsch S, Dikow N, Hasselblatt M, Schüller U, Gerber NU, White CL, Buntine MK, Kinross K, Algar EM, Hansford JR, Gottardo NG, Hernáiz Driever P, Gnekow A, Witt O, Müller HL, Calaminus G, Fleischhack G, Kordes U, Mynarek M, Rutkowski S, Frühwald MC, Kramm CM, von Deimling A, Pietsch T*, Sahm F*, Pfister SM*, Jones DTW*. Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology. Nature Med. 2023 March 16. doi: 10.1038/s41591-023-02255-1. Online ahead of print.
  • Jones DTW, Banito A, Grünewald TGP, Haber M, Jäger N, Kool M, Milde T, Molenaar JJ, Nabbi A, Pugh TJ, Schleiermacher G, Smith MA, Westermann F, Pfister SM. Molecular characteristics and therapeutic vulnerabilities across paediatric solid tumours. Nat Rev Cancer. 2019 Aug;19(8):420-438. doi: 10.1038/s41568-019-0169-x. Epub 2019 Jul 12. Review. PMID: 31300807
  • Clarke M, Mackay A, Ismer B, Pickles JC, Tatevossian RG, Newman S, Bale TA, Stoler I, Izquierdo E, Temelso S, Carvalho DM, Molinari V, Burford A, Howell L, Virasami A, Fairchild AR, Avery A, Chalker J, Kristiansen M, Haupfear K, Dalton JD, Orisme W, Wen J, Hubank M, Kurian KM, Rowe C, Maybury M, Crosier S, Knipstein J, Schuller U, Kordes U, Kram DE, Snuderl M, Bridges L, Martin AJ, Doey LJ, Al-Sarraj S, Chandler C, Zebian B, Cairns C, Natrajan R, Boult JK, Robinson SP, Sill M, Dunkel IJ, Gilheeney SW, Rosenblum MK, Hughes D, Proszek PZ, MacDonald TJ, Preusser M, Haberler C, Slavc I, Packer R, Ng HK, Caspi S, Popovic M, Faganel Kotnik B, Wood MD, Baird L, Davare MA, Solomon DA, Olsen TK, Brandal P, Farrell M, Cryan JB, Capra M, Karremann M, Schittenhelm J, Schuhmann MU, Ebinger M, Dinjens WNM, Kerl K, Hettmer S, Pietsch T, Andreiuolo F, Driever PH, Korshunov A, Hiddingh L, Worst BC, Sturm D, Zuckermann M, Witt O, Bloom T, Mitchell C, Miele E, Colafati GS, Diomedi-Camassei F, Bailey S, Moore AS, Hassall TE, Lowis SP, Tsoli M, Cowley MJ, Ziegler DS, Karajannis MA, Aquilina K, Hargrave DR, Carceller F, Marshall LV, von Deimling A, Kramm CM, Pfister SM, Sahm F, Baker SJ, Mastronuzzi A, Carai A, Vinci M, Capper D, Popov S, Ellison DW*, Jacques TS*, Jones DTW*, Jones C*. Infant high grade gliomas comprise multiple subgroups characterized by novel targetable gene fusions and favorable outcomes. Cancer Discov. 2020 Apr 1. pii: CD-19-1030. doi: 10.1158/2159-8290.CD-19-1030. [Epub ahead of print] PMID: 32238360
  • Capper D*, Jones DTW*, Sill M*, Hovestadt V*, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, Kratz A, Wefers AK, Huang K, Pajtler KW, Schweizer L, Stichel D, Olar A, Engel NW, Lindenberg K, Harter PN, Braczynski AK, Plate KH, Dohmen H, Garvalov BK, Coras R, Hölsken A, Hewer E, Bewerunge-Hudler M, Schick M, Fischer R, Beschorner R, Schittenhelm J, Staszewski O, Wani K, Varlet P, Pages M, Temming P, Lohmann D, Selt F, Witt H, Milde T, Witt O, Aronica E, Giangaspero F, Rushing E, Scheurlen W, Geisenberger C, Rodriguez FJ, Becker A, Preusser M, Haberler C, Bjerkvig R, Cryan J, Farrell M, Deckert M, Hench J, Frank S, Serrano J, Kannan K, Tsirigos A, Brück W, Hofer S, Brehmer S, Seiz-Rosenhagen M, Hänggi D, Hans V, Rozsnoki S, Hansford JR, Kohlhof P, Kristensen BW, Lechner M, Lopes B, Mawrin C, Ketter R, Kulozik A, Khatib Z, Heppner F, Koch A, Jouvet A, Keohane C, Mühleisen H, Mueller W, Pohl U, Prinz M, Benner A, Zapatka M, Gottardo NG, Driever PH, Kramm CM, Müller HL, Rutkowski S, von Hoff K, Frühwald MC, Gnekow A, Fleischhack G, Tippelt S, Calaminus G, Monoranu CM, Perry A, Jones C, Jacques TS, Radlwimmer B, Gessi M, Pietsch T, Schramm J, Schackert G, Westphal M, Reifenberger G, Wesseling P, Weller M, Collins VP, Blümcke I, Bendszus M, Debus J, Huang A, Jabado N, Northcott PA, Paulus W, Gajjar A, Robinson GW, Taylor MD, Jaunmuktane Z, Ryzhova M, Platten M, Unterberg A, Wick W, Karajannis MA, Mittelbronn M, Acker T, Hartmann C, Aldape K, Schüller U, Buslei R, Lichter P, Kool M, Herold-Mende C, Ellison DW, Hasselblatt M, Snuderl M, Brandner S, Korshunov A, von Deimling A, Pfister SM. DNA methylation-based classification of central nervous system tumours. Nature. 2018 Mar 22;555(7697):469-474. doi: 10.1038/nature26000. Epub 2018 Mar 14. PMID: 29539639
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