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Genomic and epigenomic profiling

Having previously published some of the earliest and largest molecular profiling studies of paediatric high grade glioma and DIPG, we recently compiled a retrospective analysis of more than 1000 cases of these rare tumours.


Genomic and epigenomic profiling research project


We show that they are in fact comprised of more than 10 distinct subgroups,  ranging from infant tumours driven by single gene fusion events to hypermutant cases with some of the highest mutational burdens in human cancer. Many of these tumours have key targetable alterations, whilst others remain extremely poorly defined. 

We were biology leads for the prospective HERBY randomised phase II clinical trial, whereby despite the trial showing a lack of benefit with the addition of bevacizumab to standard chemoradiotherapy, we identified subgroups of tumours with MAPK activation to have a longer survival due to their enhanced immunogenic profile.

We are currently UK biology leads for the BIOMEDE stratified trial in DIPG, and are developing co-clinical trials to identify patient-specific drug targets and personalised resistence mechanisms.

Although our understanding of the biology of these tumours has improved dramatically in the past few years, there remain subgroups of the disease which remain understudied.

These include gliomatosis cerebri, an extremely infiltrative variant excluded from current clinical trials, and infant glioma, for which our collections have increased to more than 200 as we lead on international collaborations in the molecular study of these entities.


Selected publications:

  1. Mackay A, Burford A, Molinari V, Jones DTW, Izquierdo E, Brouwer-Visser J, Giangaspero F, Haberler C, Pietsch T, Jacques TS, Figarella-Branger D, Rodriguez D, Morgan PS, Raman P, Waanders AJ, Resnick A, Massimino M, Garre ML, Smith H, Capper D, Pfister SM, Würdinger T, Tam R, Garcia J, Das Thakur M, Vassal G, Jaspan T, Varlet P and Jones C (2018) Molecular, pathological, radiological and immune profiling of non-brainstem paediatric high grade glioma from the HERBY phase II randomised trial Cancer Cell 33(5):829-842 [PMID: 29763623]
  2. Grill J, Massimino M, Bouffet E, Azizi AA, McCowage G, Cañete A, Saran F, Le Deley M-C, Varlet P, Morgan PS, Jaspan T, Jones C, Giangaspero F, Smith H, Garcia J, Elze MC, Rousseau R, Abrey L, Hargrave D and Vassal G (2018) “A phase II, open-label, randomised, multicentre trial (HERBY) of bevacizumab in paediatric patients with newly-diagnosed high-grade glioma” J Clin Oncol 36(10):951-958 [PMID: 29412784]
  3. Mackay A, Burford A, Carvalho D, Izquierdo E, Fazal Salom J, Taylor K, Bjerke L, Clarke M, Vinci M, Nandhabalan M, Temelso S, Popov S, Molinari V, Raman P, Waanders AJ, Han HJ, Gupta S, Marshall L, Zacharoulis S, Vaidya S, Mandeville HC, Bridges LR, Martin AJ, Al-Sarraj S, Chandler C, Ng HK, Li X, Mu K, Trabelsi S, H’mida Ben-Brahim D, Kisljakov AN, Konovalov DM, Moore AS, Carcaboso AM, Sunol M, de Torres C, Cruz O, Mora J, Shats LI, Bidinotto L, Reis RM, Entz-Werle N, Farrell M, Cryan J, Crimmins D, Caird J, Pears J, Monje M, Debily M-A, Castel D, Grill J, Hawkins C, Nikhbakht H, Jabado N, Baker SJ, Pfister SM, Jones DTW, Fouladi M, von Beueren AO, Baudis M, Resnick A and Jones C (2017) Integrated molecular meta-analysis of 1000 pediatric high grade glioma and diffuse intrinsic pontine glioma” Cancer Cell {Cover} 32(4):520-537 [PMID: 28966033]
  4. Bax DA*, Mackay A*, Little SE, Carvalho D, Viana -Pereira M, Tamber N, Grigoriadis A, Ashworth A,  Reis RM, Ellison DW, Al-Sarraj S, Hargrave D and Jones C (2010) “A distinct spectrum of copy number aberrations in paediatric high grade gliomas” Clin Cancer Res 16(13):3368-3377 [PMID: 20570930]
  5. Paugh BS*, Qu C*, Jones C*, Liu Z, Adamowicz-Brice M, Zhang J, Bax DA, Coyle B, Barrow J, Hargrave D, Lowe J, Gajjar A, Zhao W, Broniscer A, Ellison DW, Grundy R and Baker SJ (2010) “Integrated molecular genetic profiling of paediatric high grade gliomas reveals key differences with the adult disease” J Clin Oncol 28(18):3061-3068 [PMID: 20479398]
  6. Jones C and Baker SJ (2014) “Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma” Nature Rev Cancer 14(10):651-661 {Review} {Cover} [PMID: 25230881]