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Article: Spatial heterogeneity in medulloblastoma

TitleSpatial heterogeneity in medulloblastoma
Authors
Issue Date2017
Citation
Nature Genetics, 2017, v. 49, n. 5, p. 780-788 How to Cite?
AbstractSpatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor, which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.
Persistent Identifierhttp://hdl.handle.net/10722/313994
ISSN
2023 Impact Factor: 31.7
2023 SCImago Journal Rankings: 17.300
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMorrissy, A. Sorana-
dc.contributor.authorCavalli, Florence M.G.-
dc.contributor.authorRemke, Marc-
dc.contributor.authorRamaswamy, Vijay-
dc.contributor.authorShih, David J.H.-
dc.contributor.authorHolgado, Borja L.-
dc.contributor.authorFarooq, Hamza-
dc.contributor.authorDonovan, Laura K.-
dc.contributor.authorGarzia, Livia-
dc.contributor.authorAgnihotri, Sameer-
dc.contributor.authorKiehna, Erin N.-
dc.contributor.authorMercier, Eloi-
dc.contributor.authorMayoh, Chelsea-
dc.contributor.authorPapillon-Cavanagh, Simon-
dc.contributor.authorNikbakht, Hamid-
dc.contributor.authorGayden, Tenzin-
dc.contributor.authorTorchia, Jonathon-
dc.contributor.authorPicard, Daniel-
dc.contributor.authorMerino, Diana M.-
dc.contributor.authorVladoiu, Maria-
dc.contributor.authorLuu, Betty-
dc.contributor.authorWu, Xiaochong-
dc.contributor.authorDaniels, Craig-
dc.contributor.authorHorswell, Stuart-
dc.contributor.authorThompson, Yuan Yao-
dc.contributor.authorHovestadt, Volker-
dc.contributor.authorNorthcott, Paul A.-
dc.contributor.authorJones, David T.W.-
dc.contributor.authorPeacock, John-
dc.contributor.authorWang, Xin-
dc.contributor.authorMack, Stephen C.-
dc.contributor.authorReimand, Jüri-
dc.contributor.authorAlbrecht, Steffen-
dc.contributor.authorFontebasso, Adam M.-
dc.contributor.authorThiessen, Nina-
dc.contributor.authorLi, Yisu-
dc.contributor.authorSchein, Jacqueline E.-
dc.contributor.authorLee, Darlene-
dc.contributor.authorCarlsen, Rebecca-
dc.contributor.authorMayo, Michael-
dc.contributor.authorTse, Kane-
dc.contributor.authorTam, Angela-
dc.contributor.authorDhalla, Noreen-
dc.contributor.authorAlly, Adrian-
dc.contributor.authorChuah, Eric-
dc.contributor.authorCheng, Young-
dc.contributor.authorPlettner, Patrick-
dc.contributor.authorLi, Haiyan I.-
dc.contributor.authorCorbett, Richard D.-
dc.contributor.authorWong, Tina-
dc.contributor.authorLong, William-
dc.contributor.authorLoukides, James-
dc.contributor.authorBuczkowicz, Pawel-
dc.contributor.authorHawkins, Cynthia E.-
dc.contributor.authorTabori, Uri-
dc.contributor.authorRood, Brian R.-
dc.contributor.authorMyseros, John S.-
dc.contributor.authorPacker, Roger J.-
dc.contributor.authorKorshunov, Andrey-
dc.contributor.authorLichter, Peter-
dc.contributor.authorKool, Marcel-
dc.contributor.authorPfister, Stefan M.-
dc.contributor.authorSchüller, Ulrich-
dc.contributor.authorDirks, Peter-
dc.contributor.authorHuang, Annie-
dc.contributor.authorBouffet, Eric-
dc.contributor.authorRutka, James T.-
dc.contributor.authorBader, Gary D.-
dc.contributor.authorSwanton, Charles-
dc.contributor.authorMa, Yusanne-
dc.contributor.authorMoore, Richard A.-
dc.contributor.authorMungall, Andrew J.-
dc.contributor.authorMajewski, Jacek-
dc.contributor.authorJones, Steven J.M.-
dc.contributor.authorDas, Sunit-
dc.contributor.authorMalkin, David-
dc.contributor.authorJabado, Nada-
dc.contributor.authorMarra, Marco A.-
dc.contributor.authorTaylor, Michael D.-
dc.date.accessioned2022-07-06T11:28:47Z-
dc.date.available2022-07-06T11:28:47Z-
dc.date.issued2017-
dc.identifier.citationNature Genetics, 2017, v. 49, n. 5, p. 780-788-
dc.identifier.issn1061-4036-
dc.identifier.urihttp://hdl.handle.net/10722/313994-
dc.description.abstractSpatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor, which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.-
dc.languageeng-
dc.relation.ispartofNature Genetics-
dc.titleSpatial heterogeneity in medulloblastoma-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ng.3838-
dc.identifier.pmid28394352-
dc.identifier.pmcidPMC5553617-
dc.identifier.scopuseid_2-s2.0-85017216540-
dc.identifier.volume49-
dc.identifier.issue5-
dc.identifier.spage780-
dc.identifier.epage788-
dc.identifier.eissn1546-1718-
dc.identifier.isiWOS:000400051400018-

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