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Article: Divergent clonal selection dominates medulloblastoma at recurrence

TitleDivergent clonal selection dominates medulloblastoma at recurrence
Authors
Morrissy, A. SoranaGarzia, LiviaShih, David J.H.Zuyderduyn, ScottHuang, XiSkowron, PatrykRemke, MarcCavalli, Florence M.G.Ramaswamy, VijayLindsay, Patricia E.Jelveh, SalomehZhao, YongjunFaria, Claudia C.Pimentel, JoséNunes, SofiaShalaby, TarekGrotzer, MichaelPollack, Ian F.Hamilton, Ronald L.Li, Xiao NanBendel, Anne E.Kim, Seung KiFults, Daniel W.Walter, Andrew W.Kumabe, ToshihiroTominaga, TeijiCollins, V. PeterCho, Yoon JaeHoffman, CaitlinLyden, DavidWisoff, Jeffrey H.Garvin, James H.Cho, Byung KyuStearns, Duncan S.Massimi, LucaSchüller, UlrichSterba, JaroslavZitterbart, KarelPuget, StephanieAyrault, OlivierDunn, Sandra E.Tirapelli, Daniela P.C.Carlotti, Carlos G.Pietsch, TorstenWheeler, HelenHallahan, Andrew R.Ingram, WendyMacDonald, Tobey J.Olson, Jeffrey J.Van Meir, Erwin G.Lee, Ji YeounWang, Kyu ChangFleischhack, GudrunTippelt, StephanRa, Young ShinBailey, SimonLindsey, Janet C.Clifford, Steven C.Eberhart, Charles G.Donovan, Laura K.Cooper, Michael K.Packer, Roger J.Massimino, MauraGarre, Maria LuisaBartels, UteTabori, UriHawkins, Cynthia E.Dirks, PeterBouffet, EricRutka, James T.Wang, XinWechsler-Reya, Robert J.Weiss, William A.Collier, Lara S.Dupuy, Adam J.Korshunov, AndreyJones, David T.W.Kool, MarcelNorthcott, Paul A.Pfister, Stefan M.Largaespada, David A.Luu, BettyMungall, Andrew J.Moore, Richard A.Jabado, NadaBader, Gary D.Jones, Steven J.M.Malkin, DavidMarra, Marco A.Taylor, Michael D.Zayne, KoryLi, YisuMayoh, ChelseaThiessen, NinaMercier, EloiMungall, Karen L.Ma, YusanneTse, KaneZeng, ThomasShumansky, KareyRoth, Andrew J.L.Shah, SohrabFarooq, HamzaKijima, NoriyukiHolgado, Borja L.Lee, John J.Y.Matan-Lithwick, StuartLiu, JessicaMack, Stephen C.Manno, AlexMichealraj, K. A.Nor, CarolinaPeacock, JohnQin, LeiReimand, JuriRolider, AdiThompson, Yuan Y.Wu, XiaochongPugh, TrevorAlly, AdrianBilenky, MikhailButterfield, Yaron S.N.Carlsen, RebeccaCheng, YoungChuah, EricCorbett, Richard D.Dhalla, NoreenHe, AnLee, DarleneLi, Haiyan I.Long, WilliamMayo, MichaelPlettner, PatrickQian, Jenny Q.Schein, Jacqueline E.Tam, AngelaWong, TinaBirol, Inanc
Issue Date2016
Citation
Nature, 2016, v. 529, n. 7586, p. 351-357 How to Cite?
AbstractThe development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
Persistent Identifierhttp://hdl.handle.net/10722/313993
ISSN
2023 Impact Factor: 50.5
2023 SCImago Journal Rankings: 18.509
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMorrissy, A. Sorana-
dc.contributor.authorGarzia, Livia-
dc.contributor.authorShih, David J.H.-
dc.contributor.authorZuyderduyn, Scott-
dc.contributor.authorHuang, Xi-
dc.contributor.authorSkowron, Patryk-
dc.contributor.authorRemke, Marc-
dc.contributor.authorCavalli, Florence M.G.-
dc.contributor.authorRamaswamy, Vijay-
dc.contributor.authorLindsay, Patricia E.-
dc.contributor.authorJelveh, Salomeh-
dc.contributor.authorZhao, Yongjun-
dc.contributor.authorFaria, Claudia C.-
dc.contributor.authorPimentel, José-
dc.contributor.authorNunes, Sofia-
dc.contributor.authorShalaby, Tarek-
dc.contributor.authorGrotzer, Michael-
dc.contributor.authorPollack, Ian F.-
dc.contributor.authorHamilton, Ronald L.-
dc.contributor.authorLi, Xiao Nan-
dc.contributor.authorBendel, Anne E.-
dc.contributor.authorKim, Seung Ki-
dc.contributor.authorFults, Daniel W.-
dc.contributor.authorWalter, Andrew W.-
dc.contributor.authorKumabe, Toshihiro-
dc.contributor.authorTominaga, Teiji-
dc.contributor.authorCollins, V. Peter-
dc.contributor.authorCho, Yoon Jae-
dc.contributor.authorHoffman, Caitlin-
dc.contributor.authorLyden, David-
dc.contributor.authorWisoff, Jeffrey H.-
dc.contributor.authorGarvin, James H.-
dc.contributor.authorCho, Byung Kyu-
dc.contributor.authorStearns, Duncan S.-
dc.contributor.authorMassimi, Luca-
dc.contributor.authorSchüller, Ulrich-
dc.contributor.authorSterba, Jaroslav-
dc.contributor.authorZitterbart, Karel-
dc.contributor.authorPuget, Stephanie-
dc.contributor.authorAyrault, Olivier-
dc.contributor.authorDunn, Sandra E.-
dc.contributor.authorTirapelli, Daniela P.C.-
dc.contributor.authorCarlotti, Carlos G.-
dc.contributor.authorPietsch, Torsten-
dc.contributor.authorWheeler, Helen-
dc.contributor.authorHallahan, Andrew R.-
dc.contributor.authorIngram, Wendy-
dc.contributor.authorMacDonald, Tobey J.-
dc.contributor.authorOlson, Jeffrey J.-
dc.contributor.authorVan Meir, Erwin G.-
dc.contributor.authorLee, Ji Yeoun-
dc.contributor.authorWang, Kyu Chang-
dc.contributor.authorFleischhack, Gudrun-
dc.contributor.authorTippelt, Stephan-
dc.contributor.authorRa, Young Shin-
dc.contributor.authorBailey, Simon-
dc.contributor.authorLindsey, Janet C.-
dc.contributor.authorClifford, Steven C.-
dc.contributor.authorEberhart, Charles G.-
dc.contributor.authorDonovan, Laura K.-
dc.contributor.authorCooper, Michael K.-
dc.contributor.authorPacker, Roger J.-
dc.contributor.authorMassimino, Maura-
dc.contributor.authorGarre, Maria Luisa-
dc.contributor.authorBartels, Ute-
dc.contributor.authorTabori, Uri-
dc.contributor.authorHawkins, Cynthia E.-
dc.contributor.authorDirks, Peter-
dc.contributor.authorBouffet, Eric-
dc.contributor.authorRutka, James T.-
dc.contributor.authorWang, Xin-
dc.contributor.authorWechsler-Reya, Robert J.-
dc.contributor.authorWeiss, William A.-
dc.contributor.authorCollier, Lara S.-
dc.contributor.authorDupuy, Adam J.-
dc.contributor.authorKorshunov, Andrey-
dc.contributor.authorJones, David T.W.-
dc.contributor.authorKool, Marcel-
dc.contributor.authorNorthcott, Paul A.-
dc.contributor.authorPfister, Stefan M.-
dc.contributor.authorLargaespada, David A.-
dc.contributor.authorLuu, Betty-
dc.contributor.authorMungall, Andrew J.-
dc.contributor.authorMoore, Richard A.-
dc.contributor.authorJabado, Nada-
dc.contributor.authorBader, Gary D.-
dc.contributor.authorJones, Steven J.M.-
dc.contributor.authorMalkin, David-
dc.contributor.authorMarra, Marco A.-
dc.contributor.authorTaylor, Michael D.-
dc.contributor.authorZayne, Kory-
dc.contributor.authorLi, Yisu-
dc.contributor.authorMayoh, Chelsea-
dc.contributor.authorThiessen, Nina-
dc.contributor.authorMercier, Eloi-
dc.contributor.authorMungall, Karen L.-
dc.contributor.authorMa, Yusanne-
dc.contributor.authorTse, Kane-
dc.contributor.authorZeng, Thomas-
dc.contributor.authorShumansky, Karey-
dc.contributor.authorRoth, Andrew J.L.-
dc.contributor.authorShah, Sohrab-
dc.contributor.authorFarooq, Hamza-
dc.contributor.authorKijima, Noriyuki-
dc.contributor.authorHolgado, Borja L.-
dc.contributor.authorLee, John J.Y.-
dc.contributor.authorMatan-Lithwick, Stuart-
dc.contributor.authorLiu, Jessica-
dc.contributor.authorMack, Stephen C.-
dc.contributor.authorManno, Alex-
dc.contributor.authorMichealraj, K. A.-
dc.contributor.authorNor, Carolina-
dc.contributor.authorPeacock, John-
dc.contributor.authorQin, Lei-
dc.contributor.authorReimand, Juri-
dc.contributor.authorRolider, Adi-
dc.contributor.authorThompson, Yuan Y.-
dc.contributor.authorWu, Xiaochong-
dc.contributor.authorPugh, Trevor-
dc.contributor.authorAlly, Adrian-
dc.contributor.authorBilenky, Mikhail-
dc.contributor.authorButterfield, Yaron S.N.-
dc.contributor.authorCarlsen, Rebecca-
dc.contributor.authorCheng, Young-
dc.contributor.authorChuah, Eric-
dc.contributor.authorCorbett, Richard D.-
dc.contributor.authorDhalla, Noreen-
dc.contributor.authorHe, An-
dc.contributor.authorLee, Darlene-
dc.contributor.authorLi, Haiyan I.-
dc.contributor.authorLong, William-
dc.contributor.authorMayo, Michael-
dc.contributor.authorPlettner, Patrick-
dc.contributor.authorQian, Jenny Q.-
dc.contributor.authorSchein, Jacqueline E.-
dc.contributor.authorTam, Angela-
dc.contributor.authorWong, Tina-
dc.contributor.authorBirol, Inanc-
dc.date.accessioned2022-07-06T11:28:46Z-
dc.date.available2022-07-06T11:28:46Z-
dc.date.issued2016-
dc.identifier.citationNature, 2016, v. 529, n. 7586, p. 351-357-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10722/313993-
dc.description.abstractThe development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.-
dc.languageeng-
dc.relation.ispartofNature-
dc.titleDivergent clonal selection dominates medulloblastoma at recurrence-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/nature16478-
dc.identifier.pmid26760213-
dc.identifier.pmcidPMC4936195-
dc.identifier.scopuseid_2-s2.0-84955506668-
dc.identifier.volume529-
dc.identifier.issue7586-
dc.identifier.spage351-
dc.identifier.epage357-
dc.identifier.eissn1476-4687-
dc.identifier.isiWOS:000368354800037-
dc.identifier.f1000726072250-

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