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OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib

Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare neoplasms of the central nervous system. We describe the generation of patient-derived models from a DLGNT that metastasized to the peritoneal cavity via a ventriculoperitoneal shunt in a child. The original tumor contained a KIAA1549:BRAF...

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Autores principales: Messiaen, Julie, Claeys, Annelies, Shetty, Aniket, Spans, Lien, Derweduwe, Marleen, Uyttebroeck, Anne, Depreitere, Bart, Bempt, Isabelle Vanden, Sciot, Raf, Ligon, Keith, Jones, David, Jacobs, Sandra, De Smet, Frederik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164998/
http://dx.doi.org/10.1093/neuonc/noac079.577
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author Messiaen, Julie
Claeys, Annelies
Shetty, Aniket
Spans, Lien
Derweduwe, Marleen
Uyttebroeck, Anne
Depreitere, Bart
Bempt, Isabelle Vanden
Sciot, Raf
Ligon, Keith
Jones, David
Jacobs, Sandra
De Smet, Frederik
author_facet Messiaen, Julie
Claeys, Annelies
Shetty, Aniket
Spans, Lien
Derweduwe, Marleen
Uyttebroeck, Anne
Depreitere, Bart
Bempt, Isabelle Vanden
Sciot, Raf
Ligon, Keith
Jones, David
Jacobs, Sandra
De Smet, Frederik
author_sort Messiaen, Julie
collection PubMed
description Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare neoplasms of the central nervous system. We describe the generation of patient-derived models from a DLGNT that metastasized to the peritoneal cavity via a ventriculoperitoneal shunt in a child. The original tumor contained a KIAA1549:BRAF fusion with a chromosome 1p deletion and corresponded with methylation subclass DLGNT-MC-2 From a sample of ascitic fluid, metastatic tumoral cells could be extracted and expanded ex vivo into a long-term cell culture model. This patient-derived cell line (PDCL) showed mixed morphological phenotypes and expressed MAP2 and SYP. The KIAA1549:BRAF fusion was preserved and the PDCL still corresponded to the original methylation subclass DLGNT-MC-2. Whole-genome sequencing showed additional mutations potentially contributing to the malignant behavior of the tumor. Cytotoxic assays performed on the PDCL indicated high sensitivity to vinblastine and trametinib (MEK-inhibitor) and intermediate sensitivity to DRD/ClpP-modulators. The PDCL underwent viral transduction to induce GFP-fLux positivity and was intraperitoneally injected into immunocompromised mice. A mouse model could be generated, with the growth of a peritoneal tumor in a localized manner. The cells grown from the mouse tumor were again put into culture and were afterwards subjected to the same treatments as the PDCL. This confirmed a similar profile, with high sensitivity to vinblastin and trametinib and an intermediate sensitivity to the DRD/ClpP-modulators. In conclusion, we were able to generate patient-derived models from a metastatic DLGNT, which recapitulate the molecular characteristics of the original tumor. The models showed high sensitivity to vinblastin and targeted therapy with MEK-inhibition, but further studies are necessary to define the adequate treatment for this kind of tumor.
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spelling pubmed-91649982022-06-05 OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib Messiaen, Julie Claeys, Annelies Shetty, Aniket Spans, Lien Derweduwe, Marleen Uyttebroeck, Anne Depreitere, Bart Bempt, Isabelle Vanden Sciot, Raf Ligon, Keith Jones, David Jacobs, Sandra De Smet, Frederik Neuro Oncol Others (Not Fitting Any Other Category) Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare neoplasms of the central nervous system. We describe the generation of patient-derived models from a DLGNT that metastasized to the peritoneal cavity via a ventriculoperitoneal shunt in a child. The original tumor contained a KIAA1549:BRAF fusion with a chromosome 1p deletion and corresponded with methylation subclass DLGNT-MC-2 From a sample of ascitic fluid, metastatic tumoral cells could be extracted and expanded ex vivo into a long-term cell culture model. This patient-derived cell line (PDCL) showed mixed morphological phenotypes and expressed MAP2 and SYP. The KIAA1549:BRAF fusion was preserved and the PDCL still corresponded to the original methylation subclass DLGNT-MC-2. Whole-genome sequencing showed additional mutations potentially contributing to the malignant behavior of the tumor. Cytotoxic assays performed on the PDCL indicated high sensitivity to vinblastine and trametinib (MEK-inhibitor) and intermediate sensitivity to DRD/ClpP-modulators. The PDCL underwent viral transduction to induce GFP-fLux positivity and was intraperitoneally injected into immunocompromised mice. A mouse model could be generated, with the growth of a peritoneal tumor in a localized manner. The cells grown from the mouse tumor were again put into culture and were afterwards subjected to the same treatments as the PDCL. This confirmed a similar profile, with high sensitivity to vinblastin and trametinib and an intermediate sensitivity to the DRD/ClpP-modulators. In conclusion, we were able to generate patient-derived models from a metastatic DLGNT, which recapitulate the molecular characteristics of the original tumor. The models showed high sensitivity to vinblastin and targeted therapy with MEK-inhibition, but further studies are necessary to define the adequate treatment for this kind of tumor. Oxford University Press 2022-06-03 /pmc/articles/PMC9164998/ http://dx.doi.org/10.1093/neuonc/noac079.577 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Others (Not Fitting Any Other Category)
Messiaen, Julie
Claeys, Annelies
Shetty, Aniket
Spans, Lien
Derweduwe, Marleen
Uyttebroeck, Anne
Depreitere, Bart
Bempt, Isabelle Vanden
Sciot, Raf
Ligon, Keith
Jones, David
Jacobs, Sandra
De Smet, Frederik
OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib
title OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib
title_full OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib
title_fullStr OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib
title_full_unstemmed OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib
title_short OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib
title_sort othr-39. extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib
topic Others (Not Fitting Any Other Category)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164998/
http://dx.doi.org/10.1093/neuonc/noac079.577
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