Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information

Undifferentiated solid tumors with small blue round cell histology and expression of CD99 mostly resemble Ewing sarcoma. However, they also may include other tumors such as mesenchymal chondrosarcoma, synovial sarcoma, or small cell osteosarcoma. Definitive classification usually requires detection...

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Autores: Koelsche, Christian, Hartmann, Wolfgang, Schrimpf, Daniel, Stichel, Damian, Jabar, Susanne, Ranft, Andreas, Reuss, David E., Sahm, Felix, Jones, David T. W., Bewerunge-Hudler, Melanie, Trautmann, Marcel, Klingebiel, Thomas, Vokuhl, Christian, Gessler, Manfred, Wardelmann, Eva, Petersen, Iver, Baumhoer, Daniel, Flucke, Uta, Antonescu, Cristina, Esteller, Manel, Fröhling, Stefan, Kool, Marcel, Pfister, Stefan M., Mechtersheimer, Gunhild, Dirksen, Uta, von Deimling, Andreas
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/172427
Acesso em linha:https://hdl.handle.net/2445/172427
Access Level:acceso abierto
Palavra-chave:Sarcoma d'Ewing
Tumors
Ewing's sarcoma
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spelling Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic informationKoelsche, ChristianHartmann, WolfgangSchrimpf, DanielStichel, DamianJabar, SusanneRanft, AndreasReuss, David E.Sahm, FelixJones, David T. W.Bewerunge-Hudler, MelanieTrautmann, MarcelKlingebiel, ThomasVokuhl, ChristianGessler, ManfredWardelmann, EvaPetersen, IverBaumhoer, DanielFlucke, UtaAntonescu, CristinaEsteller, ManelFröhling, StefanKool, MarcelPfister, Stefan M.Mechtersheimer, GunhildDirksen, Utavon Deimling, AndreasSarcoma d'EwingTumorsEwing's sarcomaTumorsUndifferentiated solid tumors with small blue round cell histology and expression of CD99 mostly resemble Ewing sarcoma. However, they also may include other tumors such as mesenchymal chondrosarcoma, synovial sarcoma, or small cell osteosarcoma. Definitive classification usually requires detection of entity-specific mutations. While this approach identifies the majority of Ewing sarcomas, a subset of lesions remains unclassified and, therefore, has been termed 'Ewing-like sarcomas' or small blue round cell tumors not otherwise specified. We developed an approach for further characterization of small blue round cell tumors not otherwise specified using an array-based DNA-methylation profiling approach. Data were analyzed by unsupervised clustering and t-distributed stochastic neighbor embedding analysis and compared with a reference methylation data set of 460 well-characterized prototypical sarcomas encompassing 18 subtypes. Verification was performed by additional FISH analyses, RNA sequencing from formalin-fixed paraffin-embedded material or immunohistochemical marker analyses. In a cohort of more than 1,000 tumors assumed to represent Ewing sarcomas, 30 failed to exhibit the typical EWS translocation. These tumors were subjected to methylation profiling and could be assigned to Ewing sarcoma in 14 (47%), to small blue round cell tumors with CIC alteration in 6 (20%), to small blue round cell tumors with BCOR alteration in 4 (13%), to synovial sarcoma and to malignant rhabdoid tumor in 2 cases each. One single case each was allotted to mesenchymal chondrosarcoma and adamantinoma. 12/14 tumors classified as Ewing sarcoma could be verified by demonstrating either a canonical EWS translocation evading initial testing, by identifying rare breakpoints or fusion partners. The methylation-based assignment of the remaining small blue round cell tumors not otherwise specified also could be verified by entity-specific molecular alterations in 13/16 cases. In conclusion, array-based DNA-methylation analysis of undifferentiated tumors with small blue round cell histology is a powerful tool for precisely classifying this diagnostically challenging tumor group.Nature Publishing Group2020202020182020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion11 p.application/pdfhttps://hdl.handle.net/2445/172427Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1038/s41379-018-0045-3Modern Pathology, 2018, vol. 31, num. 8, p. 1246-1256https://doi.org/10.1038/s41379-018-0045-3(c) Koelsche, Christian et al., 2018info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1724272026-05-29T05:05:01Z
dc.title.none.fl_str_mv Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information
title Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information
spellingShingle Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information
Koelsche, Christian
Sarcoma d'Ewing
Tumors
Ewing's sarcoma
Tumors
title_short Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information
title_full Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information
title_fullStr Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information
title_full_unstemmed Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information
title_sort Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information
dc.creator.none.fl_str_mv Koelsche, Christian
Hartmann, Wolfgang
Schrimpf, Daniel
Stichel, Damian
Jabar, Susanne
Ranft, Andreas
Reuss, David E.
Sahm, Felix
Jones, David T. W.
Bewerunge-Hudler, Melanie
Trautmann, Marcel
Klingebiel, Thomas
Vokuhl, Christian
Gessler, Manfred
Wardelmann, Eva
Petersen, Iver
Baumhoer, Daniel
Flucke, Uta
Antonescu, Cristina
Esteller, Manel
Fröhling, Stefan
Kool, Marcel
Pfister, Stefan M.
Mechtersheimer, Gunhild
Dirksen, Uta
von Deimling, Andreas
author Koelsche, Christian
author_facet Koelsche, Christian
Hartmann, Wolfgang
Schrimpf, Daniel
Stichel, Damian
Jabar, Susanne
Ranft, Andreas
Reuss, David E.
Sahm, Felix
Jones, David T. W.
Bewerunge-Hudler, Melanie
Trautmann, Marcel
Klingebiel, Thomas
Vokuhl, Christian
Gessler, Manfred
Wardelmann, Eva
Petersen, Iver
Baumhoer, Daniel
Flucke, Uta
Antonescu, Cristina
Esteller, Manel
Fröhling, Stefan
Kool, Marcel
Pfister, Stefan M.
Mechtersheimer, Gunhild
Dirksen, Uta
von Deimling, Andreas
author_role author
author2 Hartmann, Wolfgang
Schrimpf, Daniel
Stichel, Damian
Jabar, Susanne
Ranft, Andreas
Reuss, David E.
Sahm, Felix
Jones, David T. W.
Bewerunge-Hudler, Melanie
Trautmann, Marcel
Klingebiel, Thomas
Vokuhl, Christian
Gessler, Manfred
Wardelmann, Eva
Petersen, Iver
Baumhoer, Daniel
Flucke, Uta
Antonescu, Cristina
Esteller, Manel
Fröhling, Stefan
Kool, Marcel
Pfister, Stefan M.
Mechtersheimer, Gunhild
Dirksen, Uta
von Deimling, Andreas
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Sarcoma d'Ewing
Tumors
Ewing's sarcoma
Tumors
topic Sarcoma d'Ewing
Tumors
Ewing's sarcoma
Tumors
description Undifferentiated solid tumors with small blue round cell histology and expression of CD99 mostly resemble Ewing sarcoma. However, they also may include other tumors such as mesenchymal chondrosarcoma, synovial sarcoma, or small cell osteosarcoma. Definitive classification usually requires detection of entity-specific mutations. While this approach identifies the majority of Ewing sarcomas, a subset of lesions remains unclassified and, therefore, has been termed 'Ewing-like sarcomas' or small blue round cell tumors not otherwise specified. We developed an approach for further characterization of small blue round cell tumors not otherwise specified using an array-based DNA-methylation profiling approach. Data were analyzed by unsupervised clustering and t-distributed stochastic neighbor embedding analysis and compared with a reference methylation data set of 460 well-characterized prototypical sarcomas encompassing 18 subtypes. Verification was performed by additional FISH analyses, RNA sequencing from formalin-fixed paraffin-embedded material or immunohistochemical marker analyses. In a cohort of more than 1,000 tumors assumed to represent Ewing sarcomas, 30 failed to exhibit the typical EWS translocation. These tumors were subjected to methylation profiling and could be assigned to Ewing sarcoma in 14 (47%), to small blue round cell tumors with CIC alteration in 6 (20%), to small blue round cell tumors with BCOR alteration in 4 (13%), to synovial sarcoma and to malignant rhabdoid tumor in 2 cases each. One single case each was allotted to mesenchymal chondrosarcoma and adamantinoma. 12/14 tumors classified as Ewing sarcoma could be verified by demonstrating either a canonical EWS translocation evading initial testing, by identifying rare breakpoints or fusion partners. The methylation-based assignment of the remaining small blue round cell tumors not otherwise specified also could be verified by entity-specific molecular alterations in 13/16 cases. In conclusion, array-based DNA-methylation analysis of undifferentiated tumors with small blue round cell histology is a powerful tool for precisely classifying this diagnostically challenging tumor group.
publishDate 2018
dc.date.none.fl_str_mv 2018
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/172427
url https://hdl.handle.net/2445/172427
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1038/s41379-018-0045-3
Modern Pathology, 2018, vol. 31, num. 8, p. 1246-1256
https://doi.org/10.1038/s41379-018-0045-3
dc.rights.none.fl_str_mv (c) Koelsche, Christian et al., 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Koelsche, Christian et al., 2018
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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