David T. W. Jones, PhD
Group leader "Pediatric glioma research"
Hopp Children's Cancer Center Heidelberg
Im Neuenheimer Feld 280
The Junior Research Group "Pediatric Glioma Research" headed by David T.W. Jones (PhD) is part of the DKFZ research program "Functional and Structural Genome Research". The group is mainly dedicated to the following two main research areas:
(I) The characterization and modeling of pediatric glioma and other rare pediatric brain tumor entities using state-of-the-art genomics, epigenomics, and translational research methods. Techniques such as Next Generation Sequencing (whole genome, transcriptome or epigenome sequencing) as well as CRISPR/Cas and other methods are used for the development of tumor models and preclinical screening.
(II) The development of personalized medicine applications. These are used to apply more precise diagnostic procedures depending on the individual tumor and to identify possible therapeutic target structures.
More about the group's work can be found on the DKFZ page "Pediatric Glioma Research".
In recent years, we have built a database of DNA methylation profiles which includes nearly 20,000 brain tumor samples. Based on this, we were able to use molecular brain tumor profiles to develop an algorithm for the classification of many different types of brain tumors.
We use this algorithm for the MNP 2.0 study, in which we prospectively assess the importance of detailed molecular profiling at the time of diagnosis for the precision of tumor classification and possible implications on patient care. We consistently observe a deviation of about 10% between the original histological tumor diagnosis and the molecular classification. In many cases, the difference in diagnosis would also affect the clinical management of the tumor.
This Germany-wide MNP 2.0 study, which is open to all childhood brain tumors, is being conducted in collaboration with the German Brain Tumor Reference Center (HTRZ) in Bonn.
The second major initiative, the INFORM project, is an international collaboration that uses high-throughput sequencing technology to create personalized molecular tumor profiles of patients at high risk for relapse. Through this analysis, we identify genetic changes in the recurrent tumor that are potential targets for a particular drug. This information should enable the attending physician to offer a customized therapy approach.
Another focus of our group is the (epi-) genetic analysis of pediatric gliomas. It is believed that these tumors arise from glial cells whose role it is to support neurons in the brain in a variety of ways. Different types of gliomas are characterized by different clinical and biological characteristics and rank between relatively benign (WHO grade I) and extremely malignant (WHO grade IV) on the World Health Organization's classification scale. Together, they account for more than half of all childhood brain tumors.
Our group seeks to identify genetic and epigenetic changes which characterize these tumors. We will learn more about how these tumors develop and how they can be treated more efficiently in the future. To achieve this, we use advanced technologies such as high-throughput sequencing to analyze the genome, transcriptome and study histone modifications. Naturally, we try to ensure that this research is translated into clinical benefit as quickly as possible. With this goal in mind, we also use methods such as CRISPR to develop models of these tumors which can be used for preclinical testing of new treatments.
Clarke M, Mackay A, Ismer B, et al., and 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. PMID: 32238360
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
Capper D, Jones DTW, Sill M, Hovestadt V et al, and 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
Sturm D, Pfister SM, Jones DTW. Pediatric Gliomas: Current Concepts on Diagnosis, Biology, and Clinical Management. J Clin Oncol. 2017 Jun 22:JCO2017730242. doi: 10.1200/JCO.2017.73.0242. PMID: 28640698
Bender S, Gronych J, Warnatz H-J, Hutter B, et al., and Pfister SM, Lichter P, Jones DTW Recurrent MET fusion genes represent a druggable target in paediatric glioblastoma. Nat Med. 2016 Nov;22(11):1314-1320 PMID: 27748748