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KiTZ research project

Everest

The Everest Centre for Low-grade Paediatric Brain Tumours

Low-grade brain tumours make up the largest group of tumours of the central nervous system in children, accounting for about half of all brain tumors in under-18s. In Germany and the UK combined, more than 400 children and adolescents are diagnosed every year. These tumours are caused by changes in the DNA that lead to uncontrolled growth of cells in the brain or spinal cord. The term ‘low-grade’ indicates that the tumours are relatively slow-growing, and the risk of their spreading to other parts of the body is low. Given their location, however, these tumours can still be very difficult to treat, with children often suffering life-long health problems as a result of their disease and/or from side-effects of the treatment.

At the established Everest Center for Low Grade Pediatric Brain Tumors, research groups from Berlin, London and Heidelberg (KiTZ and DKFZ) are pursuing the common goal of significantly improving our understanding of the biology of low-grade pediatric brain tumors in order to derive new treatment approaches in the long term. The Brain Tumor Charity, based in the UK) is funding and supporting the project, which was launched in 2017, and has since been extended with an additional funding period and thus a total of about 12 million Euros (£10 million) raised by the outstanding "Everest in the Alps" team.

A close relationship has been further established with the pediatric low-grade astrocytoma program at Dana-Faber Cancer Institute in Boston, USA, in order to advance knowledge and discovery with more man-power and close collaboration, but most importantly to jointly bring the knowledge to the young patients. Another important part of the project is to improve the quality of life with the disease. For this purpose, individual life situations are recorded and evaluated over a long period of time with the help of today's advanced technologies. The aim is to create an environment in which those affected and their families can lead a life worth living with the disease.

The Everest Center takes its name from this extraordinary fundraiser to raise awareness and support research on this disease by family and friends of Toby (a patient with low-grade glioma). Moved by Toby's story of suffering, a group of backcountry skiers crossed the Alps for four days each in 2015, 2018, 2019, 2020, 2022 and 2023. By the end of their mentally and physically draining trek, they had conquered an elevation gain equivalent to the height of Mount Everest (8848 m). More about their efforts can be read here. To date, the "Everest in the Alps" team has raised over 10 million British pounds in donations for the Brain Tumor Charity. On behalf of all those affected, we would like to thank them for this – THANK YOU!!!

 

Current activities

Newsletters, images, videos - everything that keeps you up to date to the work of the Everest center.

How tumour cell hibernation may affect the growth of low-grade brain tumours

Some of our most exciting findings to date are related to a cellular process called ‘oncogene-induced senescence’ (OIS). This is a mechanism in which some cells enter a dormant or hibernation state when they sense incorrect activation of a tumour-driving pathway, as a natural protective mechanism. We have known for some time that low-grade brain tumour cells often enter this dormant state, but not what might be controlling it or how it relates to overall tumour growth. We have now been able to show that chemicals released by the hibernating tumour cells are able to promote this state in their neighbours, and suppress tumour growth. Interestingly, we also saw that patients with high levels of this hibernation program in their tumour were less likely to experience a tumour recurrence – something which we now want to further test as part of an upcoming European clinical trial being led by us (the LOGGIC study). Finally, we found that a particular type of new drugs might be able to specifically kill these hibernating cells, which likely make up a large fraction of the cells in a typical low-grade brain tumour. This is important, because these dormant cells are often resistant to currently used chemotherapies, which typically kill only actively growing cells. We are now in the early stages of discussing how this could potentially be tested in a new Everest clinical trial concept.

A full list of scientific publications from our team members that have been financially supported through funding of the Everest Centre can be found at the bottom of this page.

 

  1. Bogumil H, Sill M, Schrimpf D, Ismer B, Blume C, Rahmanzade R, Hinz F, Cherkezov A, Banan R, Friedel D, Reuss DE, Selt F, Ecker J, Milde T, Pajtler KW, Schittenhelm J, Hench J, Frank S, Boldt HB, Kristensen BW, Scheie D, Melchior LC, Olesen V, Sehested A, Boué DR, Abdullaev Z, Satgunaseelan L, Kurth I, Seidlitz A, White CL, Ng HK, Shi ZF, Haberler C, Deckert M, Timmer M, Goldbrunner R, Tauziède-Espariat A, Varlet P, Brandner S, Alexandrescu S, Snuderl M, Aldape K, Korshunov A, Witt O, Herold-Mende C, Unterberg A, Wick W, Pfister SM, von Deimling A, Jones DTW, Sahm F, Sievers P.
    Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions. Acta Neuropathol. 2023 Mar 18. doi: 10.1007/s00401-023-02558-0. Online ahead of print. PMID: 36933012
     

  2. 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. Nat Med. 2023 Apr;29(4):917-926. doi: 10.1038/s41591-023-02255-1. Epub 2023 Mar 16. PMID: 36928815
     

  3. Stone TJ, Mankad K, Tan AIP, Jan W, Pickles JC, Gogou M, Chalker J, Slodkowska I, Pang E, Kristiansen M, Madhan GK, Forrest L, Hughes D, Koutroumanidou E, Mistry T, Ogunbiyi O, Ahmed SW, Cross JH, Hubank M, Hargrave D, Jacques TS.
    DNA methylation-based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification. Neuropathol Appl Neurobiol. 2023 Feb 26:e12894. doi: 10.1111/nan.12894. Online ahead of print. PMID: 36843390
     

  4. Gonzalez-Meljem JM, Ivins S, Andoniadou CL, Le Tissier P, Scambler P, Martinez-Barbera JP.
    An expression and function analysis of the CXCR4/SDF-1 signalling axis during pituitary gland development. PLoS One. 2023 Feb 17;18(2):e0280001. doi: 10.1371/journal.pone.0280001. eCollection 2023. PMID: 36800350
     

  5. Kratz CP, Smirnov D, Autry R, Jäger N, Waszak SM, Großhennig A, Berutti R, Wendorff M, Hainaut P, Pfister SM, Prokisch H, Ripperger T, Malkin D.
    Reply to Evans and Woodward. J Natl Cancer Inst. 2023 Feb 8;115(2):231-232. doi: 10.1093/jnci/djac224. PMID: 36495208
     

  1. Epigenetic profiling reveals a subset of pediatric-type glioneuronal tumors characterized by oncogenic gene fusions involving several targetable kinases.
    Sievers P, Sill M, Schrimpf D, Friedel D, Sturm D, Gardberg M, Kurian KM, Krskova L, Vicha A, Schaller T, Hagel C, Abdullaev Z, Aldape K, Jacques TS, Korshunov A, Wick W, Pfister SM, von Deimling A, Jones DTW, Sahm F.
    Acta Neuropathol. 2022 Sep 7. doi: 10.1007/s00401-022-02492-7. Online ahead of print. PMID: 36070143

  2. BH3 mimetics targeting BCL-XL impact the senescent compartment of pilocytic astrocytoma.
    Selt F, Sigaud R, Valinciute G, Sievers P, Zaman J, Alco C, Schmid S, Peterziel H, Tsai JW, Guiho R, Martínez-Barbera JP, Pusch S, Deng J, Zhai Y, van Tilburg CM, Schuhman MU, Damaty AEL, Bandopadhayay P, Herold-Mende C, von Deimling A, Pfister SM, Montero J, Capper D, Oehme I, Sahm F, Jones DTW, Witt O, Milde T. Neuro Oncol. 2022 Aug 17:noac199. doi: 10.1093/neuonc/noac199. Online ahead of print. PMID: 35977048

  3. The first-in-class ERK inhibitor ulixertinib shows promising activity in MAPK-driven pediatric low-grade glioma models.
    Sigaud R, Rösch L, Gatzweiler C, Benzel J, von Soosten L, Peterziel H, Selt F, Najafi S, Ayhan S, Gerloff XF, Hofmann N, Büdenbender I, Schmitt L, Foerster KI, Burhenne J, Haefeli WE, Korshunov A, Sahm F, van Tilburg CM, Jones DTW, Pfister SM, Knoerzer D, Kreider BL, Sauter M, Pajtler KW, Zuckermann M, Oehme I, Witt O, Milde T. Neuro Oncol. 2022 Jul 27:noac183. doi: 10.1093/neuonc/noac183. Online ahead of print. PMID: 35882450

  4. Low-grade diffusely infiltrative tumour (LGDIT), SMARCB1-mutant: A clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC.
    Hasselblatt M, Thomas C, Federico A, Bens S, Hellström M, Casar-Borota O, Kordes U, Neumann JE, Dottermusch M, Rodriguez FJ, Lo AC, Cheng S, Hendson G, Hukin J, Hartmann C, Koch A, Capper D, Siebert R, Paulus W, Nemes K, Johann PD, Frühwald MC, Kool M. Neuropathol Appl Neurobiol. 2022 Jun;48(4):e12797. doi: 10.1111/nan.12797. Epub 2022 Feb 18. PMID: 35152461

  5. Rapid-CNS2: Rapid comprehensive adaptive nanopore-sequencing of CNS tumors, a proof-of-concept study.
    Patel A, Dogan H, Payne A, Krause E, Sievers P, Schoebe N, Schrimpf D, Blume C, Stichel D, Holmes N, Euskirchen P, Hench J, Frank S, Rosenstiel-Goidts V, Ratliff M, Etminan N, Unterberg A, Dieterich C, Herold-Mende C, Pfister SM, Wick W, Loose M, von Deimling A, Sill M, Jones DTW, Schlesner M, Sahm F. Acta Neuropathol. 2022 May;143(5):609-612. doi: 10.1007/s00401-022-02415-6. Epub 2022 Mar 31. PMID: 35357562

  6. Contemporary Biological Insights and Clinical Management of Craniopharyngioma.
    Apps JR, Muller HL, Hankinson TC, Yock TI, Martinez-Barbera JP. Endocr Rev. 2022 Dec 27:bnac035. doi: 10.1210/endrev/bnac035. Online ahead of print. PMID: 36574377

  7. Heterozygous BRCA1 and BRCA2 and Mismatch Repair Gene Pathogenic Variants in Children and Adolescents With Cancer.
    Kratz CP, Smirnov D, Autry R, Jäger N, Waszak SM, Großhennig A, Berutti R, Wendorff M, Hainaut P, Pfister SM, Prokisch H, Ripperger T, Malkin D. J Natl Cancer Inst. 2022 Nov 14;114(11):1523-1532. doi: 10.1093/jnci/djac151. PMID: 35980168
     

  1. Pfister SM, Reyes-Múgica M, Chan JKC, Hasle H, Lazar AJ, Rossi S, Ferrari A,  Jarzembowski JA, Pritchard-Jones K, Hill AD, Jacques TS, Wesseling P, López Terrada D, von Deimling A, Kratz CP, Cree I, Alaggio R. A summary of the inaugural WHO Classification of Pediatric Tumors: Transitioning from the optical into the molecular era. Cancer Discovery. 2021 Dec 17. doi: 10.1158/2159-8290.CD-21-1094. PMID: 3492100

  2. Schmid S, Solomon DA, Perez E, Thieme A, Kleinschmidt-DeMasters BK, Giannini C, Reinhardt A, Asa SL, Mete O, Stichel D, Siewert C, Dittmayer C, Hasselblatt M, Paulus W, Nagel C, Harter PN, Schittenhelm J, Honegger J, Rushing E, Coras R, Pfister SM, Buslei R, Koch A, Perry A, Jones DTW, von Deimling A, Capper D, Lopes MB. Genetic and epigenetic characterization of posterior pituitary tumors. Acta Neuropathol. 2021 Dec;142(6):1025-1043. doi: 10.1007/s00401-021-02377-1. Epub 2021 Oct 18. PMID: 34661724

  3. Sievers P, Stichel D, Sill M, Schrimpf D, Sturm D, Selt F, Ecker J, Miele E, Kranendonk MEG, Tops BBJ, Kohlhof-Meinecke P, Beschorner R, Kramm CM, Hasselblatt M, Reifenberger G, Capper D, Wesseling P, Milde T, Korshunov A, Witt O, Pfister SM, Wick W, von Deimling A, Jones DTW,  Sahm F. Distribution of GOPC:ROS1 and other ROS1 fusions in glioma types. Acta Neuropathol. 2021 Sep. doi: 10.1007/s00401-021-02369-1. Online ahead of print. PMID: 34536122

  4. Alhalabi KT, Stichel D, Sievers P, Peterziel H, Sommerkamp AC, Sturm D, Wittmann A, Sill M, Jäger N, Beck P, Pajtler KW, Snuderl M, Jour G, Delorenzo M, Martin AM, Levy A, Dalvi N, Hansford JR, Gottardo NG, Uro-Coste E, Maurage CA, Godfraind C, Vandenbos F, Pietsch T, Kramm C, Filippidou M, Kattamis A, Jones C, Øra I, Mikkelsen TS, Zapotocky M, Sumerauer D, Scheie D, McCabe M, Wesseling P, Tops BBJ, Kranendonk MEG, Karajannis MA, Bouvier N, Papaemmanuil E, Dohmen H, Acker T, von Hoff K, Schmid S, Miele E, Filipski K, Kitanovski L, Krskova L, Gojo J, Haberler C, Alvaro F, Ecker J, Selt F, Milde T, Witt O, Oehme I, Kool M, von Deimling A, Korshunov A, Pfister SM, Sahm F, Jones DTW. PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum. Acta Neuropathol. 2021 Aug 21. doi: 10.1007/s00401-021-02354-8. Online ahead of print. PMID: 34417833

  5. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-1251. doi: 10.1093/neuonc/noab106. PMID: 34185076

  6. Schweizer L, Thierfelder F, Thomas C, Soschinski P, Kim HY, Jödicke R, Woltering N, Förster A, Teichmann D, Siewert C, Klein K, Schmid S, Nunninger M, Thomale UW, Onken J, Mühleisen H, Schittenhelm J, Tatagiba M, von Deimling A, Reuss DE, Solomon DA, Heppner FL, Koch A, Hartmann C, Staszewski O, Capper D. Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel-Lindau disease-related tumours. Neuropathol Appl Neurobiol. 2021 Jun 5. doi: 10.1111/nan.12741. Online ahead of print. PMID: 34091929

  7. Milde T, Rodriguez FJ, Barnholtz-Sloan JS, Patil N, Eberhart CG, Gutmann DH. Reimagining Pilocytic Astrocytomas in the Context of Pediatric Low-Grade Gliomas.
    Neuro Oncol. 2021 Jun 16:noab138. Online ahead of print. PMID: 34131743

  8. Stichel D, Schrimpf D, Sievers P, Reinhardt A, Suwala AK, Sill M, Reuss DE, Korshunov A, Casalini BM, Sommerkamp AC, Ecker J, Selt F, Sturm D, Gnekow A, Koch A, Simon M, Hernáiz Driever P, Schüller U, Capper D, van Tilburg CM, Witt O, Milde T, Pfister SM, Jones DTW, von Deimling A, Sahm F, Wefers AK. Accurate calling of KIAA1549-BRAF fusions from DNA of human brain tumours using methylation array-based copy number and gene panel sequencing data. Neuropathol Appl Neurobiol. 2021 Apr;47(3):406-414. doi: 10.1111/nan.12683. Epub 2021 Jan 17. PMID: 33336421

  9. Pickles JC, Mankad K, Aizpurua M, Paine SM, Bridges LR, Carceller F, Szychot E, Walker M, Fairchild AR, Mistry T, Ogunbiyi O, Rolland A, Stone TJ, Dryden C, Addy D, Garimberti E, Chalker J, Sahm F, Jones DT, Hargrave D, Jacques TS. A case series of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC). Neuropathol Appl Neurobiol. 2021 Apr;47(3):464-467. doi: 10.1111/nan.12680. Epub 2021 Jan 12. PMID: 33325069

  10. Li YF, Scerif F, Picker SR, Stone TJ, Pickles JC, Moulding DA, Avery A, Virasami A, Fairchild AR, Tisdall M, Harkness W, Cross JH, Hargrave D, Guillemot F, Paine SM, Yasin SA, Jacques TS. Identifying cellular signalling molecules in developmental disorders of the brain: Evidence from focal cortical dysplasia and tuberous sclerosis. Neuropathol Appl Neurobiol. 2021 Apr 2. PMID: 33797808

  11. Alves CAPF, Löbel U, Martin-Saavedra JS, Toescu S, Tsunemi MH, Teixeira SR, Mankad K, Hargrave D, Jacques TS, da Costa Leite C, Gonçalves FG, Vossough A, D'Arco F. A Diagnostic Algorithm for Posterior Fossa Tumors in Children: A Validation Study. AJNR. American Journal of Neuroradiology, 04 Mar 2021, 42(5):961-968. doi: 10.3174/ajnr.a7057. PMID: 33664107

  12. Chadda KR, Holland K, Scoffings D, Dean A, Pickles JC, Behjati S, Jacques TS, Trotman J, Tarpey P, Allinson K, Murray MJ. A rare case of paediatric astroblastoma with concomitant MN1-GTSE1 and EWSR1-PATZ1 gene fusions altering management. Genomics England Research Consortium. Neuropathology and Applied Neurobiology, 03 Feb 2021. doi: 10.1111/nan.12701. PMID: 33534137

  13. Hill CS, Khan M, Phipps K, Green K, Hargrave D, Aquilina K. Neurosurgical experience of managing optic pathway gliomas.
    Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery, 03 Feb 2021, 37(6):1917-1929. doi: 10.1007/s00381-021-05060-8 PMID: 33532921

  14. Carreno G, Guiho R, Martinez-Barbera JP. Cell senescence in neuropathology: A focus on neurodegeneration and tumours. Neuropathology and Applied Neurobiology, 01 Feb 2021, 47(3):359-378. doi: 10.1111/nan.12689. PMID: 33378554

  15. Azizi AA, Walker DA, Liu JF, Sehested A, Jaspan T, Pemp B, Simmons I, Ferner R, Grill J, Hargrave D, Driever PH, Evans DG, Opocher E, SIOPE NF1 OPG Nottingham, UK, Workshop 2014. NF1 optic pathway glioma: analyzing risk factors for visual outcome and indications to treat. Neuro-oncology, 01 Jan 2021, 23(1):100-111. doi: 10.1093/neuonc/noaa153. PMID: 32628746

  1. Campion T, Quirk B, Cooper J, Phipps K, Toescu S, Aquilina K, Green K, Hargrave D, Mankad K. Surveillance imaging of grade 1 astrocytomas in children: can duration and frequency of follow-up imaging and the use of contrast agents be reduced? Neuroradiology, 25 Nov 2020, 63(6):953-958. doi: 10.1007/s00234-020-02609-3. PMID: 33241451

  2. Ernst KJ, Okonechnikov K, Bageritz J, Mallm J-P, Wittmann A, Maaß KK, Leible S, Boutros M, Pfister SM, Zuckermann M, Jones DTW. Establishment of a simplified preparation method for single-nucleus RNA-sequencing. and its application to long-term frozen tumor tissues. bioRxiv 2020.10.23.351809; doi: 10.1101/2020.10.23.351809

  3. Boonzaier NR, Hales PW, D'Arco F, Walters BC, Kaur R, Mankad K, Cooper J, Liasis A, Smith V, O'Hare P, Hargrave D, Clark CA. Quantitative MRI demonstrates abnormalities of the third ventricle subventricular zone in neurofibromatosis type-1 and sporadic paediatric optic pathway glioma. NeuroImage. Clinical, 28 Sep 2020, 28:102447. doi: 10.1016/j.nicl.2020.102447. PMID: 33038669

  4. Grabovska Y, Mackay A, O'Hare P, Crosier S, Finetti M, Schwalbe EC, Pickles JC, Fairchild AR, Avery A, Cockle J, Hill R, Lindsey J, Hicks D, Kristiansen M, Chalker J, Anderson J, Hargrave D, Jacques TS, Straathof K, Bailey S, Jones C, Clifford SC. Williamson D. Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity.
    Nature Communications, 28 Aug 2020, 11(1):4324. doi: 10.1038/s41467-020-18070-y. PMID: 32859926

  5. Selt F, van Tilburg CM, Bison B, Sievers P, Harting I, Ecker J, Pajtler KW, Sahm F, Bahr A, Simon M, Jones DTW, Well L, Mautner VF, Capper D, Hernáiz Driever P, Gnekow A, Pfister SM, Witt O, Milde T. Response to trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol. 2020 Oct 7. doi: 10.1007/s11060-020-03640-3. Online ahead of print. PMID: 33026636

  6. Apps JR, Stache C, Gonzalez-Meljem JM, Gutteridge A, Chalker J, Jacques TS, Forshew T, Hölsken A, Martinez-Barbera JP. CTNNB1 mutations are clonal in adamantinomatous craniopharyngioma. Neuropathol Appl Neurobiol. 2020 Aug;46(5):510-514. doi: 10.1111/nan.12613. Epub 2020 Apr 2. PMID: 32125720

  7. Usta D, Sigaud R, Buhl JL, Selt F, Marquardt V, Pauck D, Jansen J, Pusch S, Ecker J, Hielscher T, Vollmer J, Sommerkamp AC, Rubner T, Hargrave D, van Tilburg CM, Pfister SM, Jones DTW, Remke M, Brummer T, Witt O, Milde T. A Cell-Based MAPK Reporter Assay Reveals Synergistic MAPK Pathway Activity Suppression by MAPK Inhibitor Combination in BRAF-Driven Pediatric Low-Grade Glioma Cells. Mol Cancer Ther. 2020 Aug;19(8):1736-1750. doi: 10.1158/1535-7163.MCT-19-1021. Epub 2020 May 25. PMID: 32451331

  8. Sommerkamp AC, Uhrig S, Stichel D, St-Onge P, Sun P, Jäger N, von Deimling A, Sahm F, Pfister SM, Korshunov A, Sinnett D, Jabado N, Wefers AK, Jones DTW. An optimized workflow to improve reliability of detection of KIAA1549:BRAF fusions from RNA sequencing data. Acta Neuropathol. 2020 May 31. doi: 10.1007/s00401-020-02167-1. [Epub ahead of print] PMID: 32476062

  9. Pickles JC, Stone TJ, Jacques TS. Methylation-based algorithms for diagnosis: experience from neuro-oncology. J Pathol. 2020 Apr;250(5):510-517. doi: 10.1002/path.5397. Epub 2020 Mar 10. PMID: 32057098

  10. Guerrero A, Guiho R, Herranz N, Uren A, Withers DJ, Martínez-Barbera JP, Tietze LF, Gil J. Galactose-modified duocarmycin prodrugs as senolytics. Aging Cell. 2020 Apr;19(4):e13133. doi: 10.1111/acel.13133. Epub 2020 Mar 16. PMID: 32175667

  11. Martinez-Barbera JP, Andoniadou CL. Biological Behaviour of Craniopharyngiomas. Neuroendocrinology. 2020;110(9-10):797-804. doi: 10.1159/000506904. Epub 2020 Mar 4. PMID: 32126562

  12. Perez E, Capper D. Invited Review: DNA methylation-based classification of paediatric brain tumours. Neuropathol Appl Neurobiol. 2020 Feb;46(1):28-47. doi: 10.1111/nan.12598. Epub 2020 Feb 19. PMID: 31955441

  1. Deng MY, Sill M, Sturm D, Stichel D, Witt H, Ecker J, Wittmann A, Schittenhelm J, Ebinger M, Schuhmann MU, Figarella-Branger D, Aronica E, Staszewski O, Preusser M, Haberler C, Lauten M, Schüller U, Hartmann C, Snuderl M, Dunham C, Jabado N, Wesseling P, Deckert M, Keyvani K, Gottardo N, Giangaspero F, von Hoff K, Ellison DW, Pietsch T, Herold Mende C, Milde T, Witt O, Kool M, Korshunov A, Wick W, von Deimling A, Pfister SM, Jones DTW, Sahm F. Diffuse Glioneuronal tumour with Oligodendroglioma-like features and Nuclear Clusters (DGONC) - a molecularly-defined glioneuronal CNS tumour class displaying recurrent monosomy 14. Neuropathol Appl Neurobiol. 2019 Dec 23. doi: 10.1111/nan.12590. [Epub ahead of print] PMID: 31867747
  2. Jones DTW, Bandopadhayay P, Jabado N. The Power of Human Cancer Genetics as Revealed by Low-Grade Gliomas. Annu Rev Genet. 2019 Dec 3;53:483-503. doi: 10.1146/annurev-genet-120417-031642. [Review] PMID: 31794268
  3. Guerrero A, Herranz N, Sun B, Wagner V, Gallage S, Guiho R, Wolter K, Pombo J, Irvine EE, Innes AJ, Birch J, Glegola J, Manshaei S, Heide D, Dharmalingam G, Harbig J, Olona A, Behmoaras J, Dauch D, Uren AG, Zender L, Vernia S, Martínez-Barbera JP, Heikenwalder M, Withers DJ, Gil J. Cardiac glycosides are broad-spectrum senolytics. Nat Metab. 2019 Nov;1(11):1074-1088. doi: 10.1038/s42255-019-0122-z. Epub 2019 Oct 21. PMID: 31799499
  4. George SL, Izquierdo E, Campbell J, Koutroumanidou E, Proszek P, Jamal S, Hughes D, Yuan L, Marshall LV, Carceller F, Chisholm JC, Vaidya S, Mandeville H, Angelini P, Wasti A, Bexelius T, Thway K, Gatz SA, Clarke M, Al-Lazikani B, Barone G, Anderson J, Tweddle DA, Gonzalez D, Walker BA, Barton J, Depani S, Eze J, Ahmed SW, Moreno L, Pearson A, Shipley J, Jones C, Hargrave D, Jacques TS, Hubank M, Chesler L. A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations. Eur J Cancer. 2019 Nov;121:224-235. doi: 10.1016/j.ejca.2019.07.027. Epub 2019 Sep 19. PMID: 31543384
  5. Pickles JC, Fairchild AR, Stone TJ, Brownlee L, Merve A, Yasin SA, Avery A, Ahmed SW, Ogunbiyi O, Gonzalez Zapata J, Peary AF, Edwards M, Wilkhu L, Dryden C, Ladon D, Kristiansen M, Rowe C, Kurian KM, Nicoll JAR, Mitchell C, Bloom T, Hilton DA, Al-Sarraj S, Doey L, Johns PN, Bridges LR, Chakrabarty A, Ismail A, Rathi N, Syed K, Lammie GA, Limback-Stanic C, Smith C, Torgersen A, Rae F, Hill RM, Clifford SC, Grabovska Y, Williamson D, Clarke M, Jones C, Capper D, Sill M, von Deimling A, Pfister SM, Jones DTW, Hargrave D, Chalker J, Jacques TS. DNA methylation-based profiling for paediatric CNS tumour diagnosis and treatment: a population-based study. Lancet Child Adolesc Health. 2019 Nov 27. pii: S2352-4642(19)30342-6. doi: 10.1016/S2352-4642(19)30342-6. [Epub ahead of print] PMID: 31786093
  6. Sievers P, Schrimpf D, Stichel D, Reuss DE, Hasselblatt M, Hagel C, Staszewski O, Hench J, Frank S, Brandner S, Korshunov A, Wick W, Pfister SM, Reifenberger G, von Deimling A, Sahm F, Jones DTW. Posterior fossa pilocytic astrocytomas with oligodendroglial features show frequent FGFR1 activation via fusion or mutation. Acta Neuropathol. 2019 Nov 15. doi: 10.1007/s00401-019-02097-7. [Epub ahead of print]. PMID: 31729570
  7. Sievers P, Appay R, Schrimpf D, Stichel D, Reuss DE, Wefers AK, Reinhardt A, Coras R, Ruf VC, Schmid S, de Stricker K, Boldt HB, Kristensen BW, Petersen JK, Ulhøi BP, Gardberg M, Aronica E, Hasselblatt M, Brück W, Bielle F, Mokhtari K, Lhermitte B, Wick W, Herold-Mende C, Hänggi D, Brandner S, Giangaspero F, Capper D, Rushing E, Wesseling P, Pfister SM, Figarella-Branger D, von Deimling A, Sahm F, Jones DTW. Rosette-forming glioneuronal tumors share a distinct DNA methylation profile and mutations in FGFR1, with recurrent co-mutation of PIK3CA and NF1. Acta Neuropathol. 2019 Sep;138(3):497-504. doi: 10.1007/s00401-019-02038-4. Epub 2019 Jun 27. PMID: 31250151
  8. Wefers AK, Stichel D, Schrimpf D, Coras R, Pages M, Tauziède-Espariat A, Varlet P, Schwarz D, Söylemezoglu F, Pohl U, Pimentel J, Meyer J, Hewer E, Japp A, Joshi A, Reuss DE, Reinhardt A, Sievers P, Casalini MB, Ebrahimi A, Huang K, Koelsche C, Low HL, Rebelo O, Marnoto D, Becker AJ, Staszewski O, Mittelbronn M, Hasselblatt M, Schittenhelm J, Cheesman E, de Oliveira RS, Queiroz RGP, Valera ET, Hans VH, Korshunov A, Olar A, Ligon KL, Pfister SM, Jaunmuktane Z, Brandner S, Tatevossian RG, Ellison DW, Jacques TS, Honavar M, Aronica E, Thom M, Sahm F, von Deimling A, Jones DTW, Blumcke I, Capper D. Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course. Acta Neuropathol. 2019 Sep 28. doi: 10.1007/s00401-019-02078-w. [Epub ahead of print] PMID: 31563982
  9. Carreno G, Boult JKR, Apps JR, Gonzalez-Meljem JM, Haston S, Guiho R, Stache C, Danielson LS, Koers A, Smith LS, Virasami A, Panousopoulos L, Buchfelder M, Jacques TS, Chesler L, Robinson S, Martinez-Barbera JP. SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma. Endocr Relat Cancer. 2019 Jan 1. pii: ERC-18-0538.R1. doi: 10.1530/ERC-18-0538. PMID:30645190
  10. Buhl JL, Selt F, Hielscher T, Guiho R, Ecker J, Sahm F, Ridinger J, Riehl D, Usta D, Ismer B, Sommerkamp AC, Martinez-Barbera JP, Wefers AK, Remke M, Picard D, Pusch S, Gronych J, Oehme I, van Tilburg CM, Kool M, Kuhn D, Capper D, von Deimling A, Schuhmann MU, Herold-Mende C, Korshunov A, Brummer T, Pfister SM, Jones DTW, Witt O, Milde T. The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma. Clin Cancer Res. 2019 Mar 15;25(6):1851-1866. doi: 10.1158/1078-0432.CCR-18-1965. Epub 2018 Dec 7. PMID: 30530705
  11. Blümcke I, Coras R, Wefers AK, Capper D, Aronica E, Becker A, Honavar M, Stone TJ, Jacques TS, Miyata H, Mühlebner A, Pimentel J, Söylemezoğlu F, Thom M. Challenges in the histopathological classification of ganglioglioma and DNT: microscopic agreement studies and a preliminary genotype-phenotype analysis. Neuropathol Appl Neurobiol. 2019 Feb;45(2):95-107. doi: 10.1111/nan.12522. Epub 2018 Dec 9. Review. PMID: 30326153
  1. Valera ET, McConechy MK, Gayden T, Rivera B, Jones DTW, Wittmann A, Han H, Bareke E, Nikbakht H, Mikael L, Queiroz RG, Suazo VK, Phi JH, Kim SK, Park SH, Fukaya R, Yum MS, Ko TS, de Oliveira RS, Machado HR, Brassesco MS, do Santos AC, Simão GN, Ramalho LNZ, Neder L, Scrideli CA, Tone LG, Majewski J, Jabado N. Methylome analysis and whole-exome sequencing reveal that brain tumors associated with encephalocraniocutaneous lipomatosis are midline pilocytic astrocytomas. Acta Neuropathol. 2018 Oct;136(4):657-660. doi: 10.1007/s00401-018-1898-8. Epub 2018 Aug 24. PMID: 30143858
  2. Reinhardt A, Stichel D, Schrimpf D, Sahm F, Korshunov A, Reuss DE, Koelsche C, Huang K, Wefers AK, Hovestadt V, Sill M, Gramatzki D, Felsberg J, Reifenberger G, Koch A, Thomale UW, Becker A, Hans VH, Prinz M, Staszewski O, Acker T, Dohmen H, Hartmann C, Mueller W, Tuffaha MSA, Paulus W, Heß K, Brokinkel B, Schittenhelm J, Monoranu CM, Kessler AF, Loehr M, Buslei R, Deckert M, Mawrin C, Kohlhof P, Hewer E, Olar A, Rodriguez FJ, Giannini C, NageswaraRao AA, Tabori U, Nunes NM, Weller M, Pohl U, Jaunmuktane Z, Brandner S, Unterberg A, Hänggi D, Platten M, Pfister SM, Wick W, Herold-Mende C, Jones DTW, von Deimling A, Capper D. Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations. Acta Neuropathol. 2018 Aug;136(2):273-291. doi: 10.1007/s00401-018-1837-8. Epub 2018 Mar 21. PMID: 29564591
  3. Sievers P, Stichel D, Schrimpf D, Sahm F, Koelsche C, Reuss DE, Wefers AK, Reinhardt A, Huang K, Ebrahimi A, Hou Y, Pajtler KW, Pfister SM, Hasselblatt M, Stummer W, Schick U, Hartmann C, Hagel C, Staszewski O, Reifenberger G, Beschorner R, Coras R, Keyvani K, Kohlhof P, Diomedi-Camassei F, Herold-Mende C, Giangaspero F, Rushing E, Giannini C, Korshunov A, Jones DTW, von Deimling A. FGFR1:TACC1 fusion is a frequent event in molecularly defined extraventricular neurocytoma. Acta Neuropathol. 2018 Jul 5. doi: 10.1007/s00401-018-1882-3. PMID: 29978331
  4. Deng MY, Sill M, Chiang J, Schittenhelm J, Ebinger M, Schuhmann MU, Monoranu CM, Milde T, Wittmann A, Hartmann C, Sommer C, Paulus W, Gärtner J, Brück W, Rüdiger T, Leipold A, Jaunmuktane Z, Brandner S, Giangaspero F, Nozza P, Mora J, Morales la Madrid A, Cruz Martinez O, Hansford JR, Pietsch T, Tietze A, Hernáiz-Driever P, Stoler I, Capper D, Korshunov A, Ellison DW, von Deimling A, Pfister SM, Sahm F, Jones DTW. Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features. Acta Neuropathol. 2018 May 15. doi: 10.1007/s00401-018-1865-4. PMID: 29766299
  5. Siegfried A, Rousseau A, Maurage CA, Pericart S, Nicaise Y, Escudie F, Grand D, Delrieu A, Gomez-Brouchet A, Le Guellec S, Franchet C, Boetto S, Vinchon M, Sol JC, Roux FE, Rigau V, Bertozzi AI, Jones DTW, Figarella-Branger D, Uro-Coste E EWSR1-PATZ1 gene fusion may define a new glioneuronal tumor entity. Brain Pathol. 2018 Apr 21. doi: 10.1111/bpa.12619. PMID: 29679497
  6. 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
  7. Apps JR, Carreno G, Gonzalez-Meljem JM, Haston S, Guiho R, Cooper JE, Manshaei S, Jani N, Hölsken A, Pettorini B, Beynon RJ, Simpson DM, Fraser HC, Hong Y, Hallang S, Stone TJ, Virasami A, Donson AM, Jones D, Aquilina K, Spoudeas H, Joshi AR, Grundy R, Storer LCD, Korbonits M, Hilton DA, Tossell K, Thavaraj S, Ungless MA, Gil J, Buslei R, Hankinson T, Hargrave D, Goding C, Andoniadou CL, Brogan P, Jacques TS, Williams HJ, Martinez-Barbera JP. Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target. Acta Neuropathol. 2018 May;135(5):757-777. doi: 10.1007/s00401-018-1830-2. Epub 2018 Mar 14. PMID: 29541918
  8. Stone TJ, Rowell R, Jayasekera BAP, Cunningham MO, Jacques TS. Review: Molecular characteristics of long-term epilepsy-associated tumours (LEATs) and mechanisms for tumour-related epilepsy (TRE). Neuropathol Appl Neurobiol. 2018 Feb;44(1):56-69. doi: 10.1111/nan.12459. Review. PMID: 29315734
  9. Stone TJ, Keeley A, Virasami A, Harkness W, Tisdall M, Izquierdo Delgado E, Gutteridge A, Brooks T, Kristiansen M, Chalker J, Wilkhu L, Mifsud W, Apps J, Thom M, Hubank M, Forshew T, Cross JH, Hargrave D, Ham J, Jacques TS. Comprehensive molecular characterisation of epilepsy-associated glioneuronal tumours. Acta Neuropathol. 2018 Jan;135(1):115-129. doi: 10.1007/s00401-017-1773-z. Epub 2017 Oct 20. PMID: 29058119
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Group
  • David T.W. Jones (KiTZ & DKFZ Heidelberg)
  • Stefan M. Pfister (KiTZ, DKFZ & University Hospital Heidelberg)
  • Olaf Witt (KiTZ, DKFZ & University Hospital Heidelberg)
  • Till Milde (KiTZ, DKFZ & University Hopital Heidelberg)
  • David Capper (DKTK & Charité Berlin)
  • Felix Sahm (KiTZ & University Hospital Heidelberg)
  • Denise Sheer (Blizard Institute, Queen Mary’s, University of London)
  • Tom Jacques (University College London/Great Ormond Street Hospital Institute of Child Health)
  • J-P Martinez-Barbera (University College London/Great Ormond Street Hospital Institute of Child Health)
  • Darren Hargrave (University College London/Great Ormond Street Hospital Institute of Child Health)

David T. W. Jones, PhD

Head of division "Pediatric glioma research"

Postal address:
Hopp Children's Cancer Center Heidelberg
Im Neuenheimer Feld 280
D-69120 Heidelberg
Germany