Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes

Pascal D. Johann; Serap Erkek; Marc Zapatka; Kornelius Kerl; Ivo Buchhalter; Volker Hovestadt; David T.W. Jones; Dominik Sturm; Carl Hermann; Maia Segura Wang; Andrey Korshunov; Marina Rhyzova; Susanne Gröbner; Sebastian Brabetz; Lukas Chavez; Susanne Bens; Stefan Gröschel; Fabian Kratochwil; Andrea Wittmann; Laura Sieber; Christina Geörg; Stefan Wolf; Katja Beck; Florian Oyen; David Capper; Peter van Sluis; Richard Volckmann; Jan Koster; Rogier Versteeg; Andreas von Deimling; Till Milde; Olaf Witt; Andreas E. Kulozik; Martin Ebinger; Tarek Shalaby; Michael Grotzer; David Sumerauer; Josef Zamecnik; Jaume Mora; Nada Jabado; Michael D. Taylor; Annie Huang; Eleonora Aronica; Anna Bertoni; Bernhard Radlwimmer; Torsten Pietsch; Ulrich Schüller; Reinhard Schneppenheim; Paul A. Northcott; Jan O. Korbel; Reiner Siebert; Michael C. Frühwald; Peter Lichter; Roland Eils; Amar Gajjar; Martin Hasselblatt; Stefan M. Pfister; Marcel Kool

doi:10.1016/j.ccell.2016.02.001

Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes

Pascal D. Johann, Serap Erkek, Marc Zapatka, Kornelius Kerl, Ivo Buchhalter, Volker Hovestadt, David T.W. Jones, Dominik Sturm, Carl Hermann, Maia Segura Wang, Andrey Korshunov, Marina Rhyzova, Susanne Gröbner, Sebastian Brabetz, Lukas Chavez, Susanne Bens, Stefan Gröschel, Fabian Kratochwil, Andrea Wittmann, Laura SieberChristina Geörg, Stefan Wolf, Katja Beck, Florian Oyen, David Capper, Peter van Sluis, Richard Volckmann, Jan Koster, Rogier Versteeg, Andreas von Deimling, Till Milde, Olaf Witt, Andreas E. Kulozik, Martin Ebinger, Tarek Shalaby, Michael Grotzer, David Sumerauer, Josef Zamecnik, Jaume Mora, Nada Jabado, Michael D. Taylor, Annie Huang, Eleonora Aronica, Anna Bertoni, Bernhard Radlwimmer, Torsten Pietsch, Ulrich Schüller, Reinhard Schneppenheim, Paul A. Northcott, Jan O. Korbel, Reiner Siebert, Michael C. Frühwald, Peter Lichter, Roland Eils, Amar Gajjar, Martin Hasselblatt, Stefan M. Pfister, Marcel Kool

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Abstract

Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.

Original language	English
Pages (from-to)	379-393
Number of pages	15
Journal	Cancer Cell
Volume	29
Issue number	3
DOIs	https://doi.org/10.1016/j.ccell.2016.02.001
Publication status	Published - 14 Mar 2016
Externally published	Yes

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10.1016/j.ccell.2016.02.001

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Johann, P. D., Erkek, S., Zapatka, M., Kerl, K., Buchhalter, I., Hovestadt, V., Jones, D. T. W., Sturm, D., Hermann, C., Segura Wang, M., Korshunov, A., Rhyzova, M., Gröbner, S., Brabetz, S., Chavez, L., Bens, S., Gröschel, S., Kratochwil, F., Wittmann, A., ... Kool, M. (2016). Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes. Cancer Cell, 29(3), 379-393. https://doi.org/10.1016/j.ccell.2016.02.001

@article{3b233d2e837e4e9283a606cd4b2b56fa,

title = "Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes",

abstract = "Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.",

author = "Johann, {Pascal D.} and Serap Erkek and Marc Zapatka and Kornelius Kerl and Ivo Buchhalter and Volker Hovestadt and Jones, {David T.W.} and Dominik Sturm and Carl Hermann and {Segura Wang}, Maia and Andrey Korshunov and Marina Rhyzova and Susanne Gr{\"o}bner and Sebastian Brabetz and Lukas Chavez and Susanne Bens and Stefan Gr{\"o}schel and Fabian Kratochwil and Andrea Wittmann and Laura Sieber and Christina Ge{\"o}rg and Stefan Wolf and Katja Beck and Florian Oyen and David Capper and {van Sluis}, Peter and Richard Volckmann and Jan Koster and Rogier Versteeg and {von Deimling}, Andreas and Till Milde and Olaf Witt and Kulozik, {Andreas E.} and Martin Ebinger and Tarek Shalaby and Michael Grotzer and David Sumerauer and Josef Zamecnik and Jaume Mora and Nada Jabado and Taylor, {Michael D.} and Annie Huang and Eleonora Aronica and Anna Bertoni and Bernhard Radlwimmer and Torsten Pietsch and Ulrich Sch{\"u}ller and Reinhard Schneppenheim and Northcott, {Paul A.} and Korbel, {Jan O.} and Reiner Siebert and Fr{\"u}hwald, {Michael C.} and Peter Lichter and Roland Eils and Amar Gajjar and Martin Hasselblatt and Pfister, {Stefan M.} and Marcel Kool",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = mar,

day = "14",

doi = "10.1016/j.ccell.2016.02.001",

language = "English",

volume = "29",

pages = "379--393",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "3",

}

Johann, PD, Erkek, S, Zapatka, M, Kerl, K, Buchhalter, I, Hovestadt, V, Jones, DTW, Sturm, D, Hermann, C, Segura Wang, M, Korshunov, A, Rhyzova, M, Gröbner, S, Brabetz, S, Chavez, L, Bens, S, Gröschel, S, Kratochwil, F, Wittmann, A, Sieber, L, Geörg, C, Wolf, S, Beck, K, Oyen, F, Capper, D, van Sluis, P, Volckmann, R, Koster, J, Versteeg, R, von Deimling, A, Milde, T, Witt, O, Kulozik, AE, Ebinger, M, Shalaby, T, Grotzer, M, Sumerauer, D, Zamecnik, J, Mora, J, Jabado, N, Taylor, MD, Huang, A, Aronica, E, Bertoni, A, Radlwimmer, B, Pietsch, T, Schüller, U, Schneppenheim, R, Northcott, PA, Korbel, JO, Siebert, R, Frühwald, MC, Lichter, P, Eils, R, Gajjar, A, Hasselblatt, M, Pfister, SM & Kool, M 2016, 'Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes', Cancer Cell, vol. 29, no. 3, pp. 379-393. https://doi.org/10.1016/j.ccell.2016.02.001

TY - JOUR

T1 - Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes

AU - Johann, Pascal D.

AU - Erkek, Serap

AU - Zapatka, Marc

AU - Kerl, Kornelius

AU - Buchhalter, Ivo

AU - Hovestadt, Volker

AU - Jones, David T.W.

AU - Sturm, Dominik

AU - Hermann, Carl

AU - Segura Wang, Maia

AU - Korshunov, Andrey

AU - Rhyzova, Marina

AU - Gröbner, Susanne

AU - Brabetz, Sebastian

AU - Chavez, Lukas

AU - Bens, Susanne

AU - Gröschel, Stefan

AU - Kratochwil, Fabian

AU - Wittmann, Andrea

AU - Sieber, Laura

AU - Geörg, Christina

AU - Wolf, Stefan

AU - Beck, Katja

AU - Oyen, Florian

AU - Capper, David

AU - van Sluis, Peter

AU - Volckmann, Richard

AU - Koster, Jan

AU - Versteeg, Rogier

AU - von Deimling, Andreas

AU - Milde, Till

AU - Witt, Olaf

AU - Kulozik, Andreas E.

AU - Ebinger, Martin

AU - Shalaby, Tarek

AU - Grotzer, Michael

AU - Sumerauer, David

AU - Zamecnik, Josef

AU - Mora, Jaume

AU - Jabado, Nada

AU - Taylor, Michael D.

AU - Huang, Annie

AU - Aronica, Eleonora

AU - Bertoni, Anna

AU - Radlwimmer, Bernhard

AU - Pietsch, Torsten

AU - Schüller, Ulrich

AU - Schneppenheim, Reinhard

AU - Northcott, Paul A.

AU - Korbel, Jan O.

AU - Siebert, Reiner

AU - Frühwald, Michael C.

AU - Lichter, Peter

AU - Eils, Roland

AU - Gajjar, Amar

AU - Hasselblatt, Martin

AU - Pfister, Stefan M.

AU - Kool, Marcel

PY - 2016/3/14

Y1 - 2016/3/14

N2 - Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.

AB - Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.

UR - http://www.scopus.com/inward/record.url?scp=84959151000&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2016.02.001

DO - 10.1016/j.ccell.2016.02.001

M3 - Article

C2 - 26923874

AN - SCOPUS:84959151000

SN - 1535-6108

VL - 29

SP - 379

EP - 393

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes

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