Molecular Diagnostics
Group Members
David T. W. Jones, PhD (Group leader)
Barbara Worst, MD (Physician Scientist, Universitätsklinikum Heidelberg)
Dominik Sturm, MD (Physician Scientist, Universitätsklinikum Heidelberg)
Elke Pfaff, MD (Physician Scientist, Universitätsklinikum Heidelberg)
Mirjam Blattner-Johnson (PostDoc)
Marc Zuckermann, PhD (Postdoc)
Britta Ismer (PhD student)
Andrea Wittmann (TA)
Agata Rode, PhD  (Project Manager)
Lotte Hiddingh, PhD  (Biotechnologist)
Maximilian Deng (MD student)
Sebastian Bender, PhD
Sonja Hutter, PhD
Translational Research Interests
A major goal of our group is to facilitate the rapid translation of basic scientific findings into applications which can be of immediate value to brain tumor patients. This is split into two main themes: Using genomics technologies as a tool to help pathologists achieve greater diagnostic accuracy; and developing ‘personalized medicine’ approaches that allow treatments to be tailored specifically to a particular patient’s disease. Through the Molecular Neuropathology program, we are developing a method that uses genome-wide DNA methylation patterns as a ‘fingerprint’ of the life history of a tumor, which can be very helpful when trying to reach a diagnosis. The accuracy of initial tumor diagnosis is very important, as it has a major impact on making sure that patients receive the optimum clinical care.
The second major initiative, the INFORM project, is a national collaboration. INFORM uses high-throughput sequencing technologies to produce personalized molecular profiles of tumors from patients with high-risk, relapsed disease. Based on this analysis, we aim to provide information about any alterations in the tumor which could potentially be targeted by a specific drug treatment. This information may be used by the treating physician to offer a more tailored therapeutic approach.
Basic Research Interests
The other key focus of this subgroup is the genomic and epigenomic analysis of pediatric gliomas, a class of brain tumors which arise from cells in the brain that support neurons. There are multiple different types of glioma, with different clinical and biological characteristics, and they range from relatively benign (World Health Organization Grade I) to highly malignant (WHO Grade IV). Together, they account for nearly half of all brain tumors in children. Our group aims to identify the genetic and epigenetic alterations which characterize these tumors, so that we can learn more about how they develop and how they may be treated more effectively in the future. To achieve this, we are using cutting-edge technologies such as high-throughput sequencing of DNA, RNA, and chromatin modifications, together with advanced computational analysis. Of course, we aim to ensure that these findings will also find a rapid path into clinical utility.
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Selected Publications
Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, 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, Łastowska 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.
Sahm F*, Schrimpf D*, Jones DTW*, Meyer J*, Kratz A, Reuss D, Capper D, Koelsche C, Korshunov A, Wiestler B, Buchhalter I, Milde T, Selt F, Sturm D, Kool M, Hummel M, Bewerunge-Hudler M, Mawrin C, Schüller U, Jungk C, Wick A, Witt O, Platten M, Herold-Mende C, Unterberg A, Pfister SM, Wick W, von Deimling A, Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets. Acta Neuropathol. 2015 Dec 15. [Epub ahead of print]
Alioto TS, Buchhalter I, Derdak S, Hutter B, Eldridge MD, Hovig E, Heisler LE, Beck TA, Simpson JT, Tonon L, Sertier AS, Patch AM, Jäger N, Ginsbach P, Drews R, Paramasivam N, Kabbe R, Chotewutmontri S, Diessl N, Previti C, Schmidt S, Brors B, Feuerbach L, Heinold M, Gröbner S, Korshunov A, Tarpey PS, Butler AP, Hinton J, Jones D, Menzies A, Raine K, Shepherd R, Stebbings L, Teague JW, Ribeca P, Giner FC, Beltran S, Raineri E, Dabad M, Heath SC, Gut M, Denroche RE, Harding NJ, Yamaguchi TN, Fujimoto A, Nakagawa H, Quesada V, Valdés-Mas R, Nakken S, Vodák D, Bower L, Lynch AG, Anderson CL, Waddell N, Pearson JV, Grimmond SM, Peto M, Spellman P, He M, Kandoth C, Lee S, Zhang J, Létourneau L, Ma S, Seth S, Torrents D, Xi L, Wheeler DA, López-Otín C, Campo E, Campbell PJ, Boutros PC, Puente XS, Gerhard DS, Pfister SM, McPherson JD, Hudson TJ, Schlesner M, Lichter P, Eils R*, Jones DTW*, Gut IG*, A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing. Nat Commun. 2015 Dec 9;6:10001
Korshunov A, Ryzhova M, Hovestadt V, Bender S, Sturm D, Capper D, Meyer J, Schrimpf D, Kool M, Northcott PA, Zheludkova O, Milde T, Witt O, Kulozik AE, Reifenberger G, Jabado N, Perry A, Lichter P, von Deimling A, Pfister SM, Jones DTW, Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathol. 2015 May 129(5):669-78
Pajtler KW, Witt H, Sill M, Jones DTW, 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
Hutter S, Piro RM, Reuss DE, Hovestadt V, Sahm F, Farschtschi S, Kehrer-Sawatzki H, Wolf S, Lichter P, von Deimling A, Schuhmann MU, Pfister SM, Jones DTW*, Mautner VF*, Whole exome sequencing reveals that the majority of schwannomatosis cases remain unexplained after excluding SMARCB1 and LZTR1 germline variants. Acta Neuropathol. 2014 Sep;128(3):449-52
Hovestadt V*, Jones DTW*, Picelli S, Wang W, Kool M, Northcott PA, Sultan M, Stachurski K, Ryzhova M, Warnatz H-J, Ralser M, Brun S, Bunt J, Jäger N, Kleinheinz K, Erkek S, Weber UD, Bartholomae CC, von Kalle C, Lawerenz C, Eils J, Koster J, Versteeg R, Milde T, Witt O, Schmidt S, Wolf S, Pietsch T, Rutkowski S, Scheurlen W, Taylor MD, Brors B, Felsberg J, Reifenberger G, Borkhardt A, Lehrach H, Wechsler-Reya RJ, Eils R, Yaspo M-L, Landgraf P, Korshunov A, Zapatka M, Radlwimmer B, Pfister SM, and Lichter P, Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing. Nature 2014 Jun 26;510(7506):537-41
Fontebasso AM, Papillon-Cavanagh S, Schwartzentruber J, Nikbakht H, Gerges N, Fiset PO, Bechet D, Faury D, De Jay N, Ramkissoon LA, Corcoran A, Jones DTW, Sturm D, Johann P, Tomita T, Goldman S, Nagib M, Bendel A, Goumnerova L, Bowers DC, Leonard JR, Rubin JB, Alden T, Browd S, Geyer JR, Leary S, Jallo G, Cohen K, Gupta N, Prados MD, Carret AS, Ellezam B, Crevier L, Klekner A, Bognar L, Hauser P, Garami M, Myseros J, Dong Z, Siegel PM, Malkin H, Ligon AH, Albrecht S, Pfister SM, Ligon KL, Majewski J, Jabado N, Kieran MW. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat Genet. 2014 May;46(5):462-6.
Kool M, Jones DTW, Jäger N, Northcott PA, Pugh TJ, Hovestadt V, Piro RM, Esparza LA, Markant SL, Remke M, Milde T, Bourdeaut F, Ryzhova M, Sturm D, Pfaff E, Stark S, Hutter S, Seker-Cin H, Johann P, Bender S, Schmidt C, Rausch T, Shih D, Reimand J, Sieber L, Wittmann A, Linke L, Witt H, Weber UD, Zapatka M, König R, Beroukhim R, Bergthold G, van Sluis P, Volckmann R, Koster J, Versteeg R, Schmidt S, Wolf S, Lawerenz C, Bartholomae CC, von Kalle C, Unterberg A, Herold-Mende C, Hofer S, Kulozik AE, von Deimling A, Scheurlen W, Felsberg J, Reifenberger G, Hasselblatt M, Crawford JR, Grant GA, Jabado N, Perry A, Cowdrey C, Croul S, Zadeh G, Korbel JO, Doz F, Delattre O, Bader GD, McCabe MG, Collins VP, Kieran MW, Cho YJ, Pomeroy SL, Witt O, Brors B, Taylor MD, Schüller U, Korshunov A, Eils R, Wechsler-Reya RJ, Lichter P, Pfister SM, Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition. Cancer Cell 2014 Mar 17;25(3):393-405