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000120652 0247_ $$2doi$$a10.1038/ng.3838
000120652 0247_ $$2pmid$$apmid:28394352
000120652 0247_ $$2ISSN$$a1061-4036
000120652 0247_ $$2ISSN$$a1546-1718
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000120652 1001_ $$aMorrissy, A Sorana$$b0
000120652 245__ $$aSpatial heterogeneity in medulloblastoma.
000120652 260__ $$aNew York, NY$$bNature America$$c2017
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000120652 520__ $$aSpatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor, which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.
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000120652 7001_ $$aCavalli, Florence M G$$b1
000120652 7001_ $$00000-0002-9404-9993$$aRemke, Marc$$b2
000120652 7001_ $$00000-0002-6557-895X$$aRamaswamy, Vijay$$b3
000120652 7001_ $$aShih, David J H$$b4
000120652 7001_ $$aHolgado, Borja L$$b5
000120652 7001_ $$aFarooq, Hamza$$b6
000120652 7001_ $$aDonovan, Laura K$$b7
000120652 7001_ $$aGarzia, Livia$$b8
000120652 7001_ $$aAgnihotri, Sameer$$b9
000120652 7001_ $$aKiehna, Erin N$$b10
000120652 7001_ $$aMercier, Eloi$$b11
000120652 7001_ $$aMayoh, Chelsea$$b12
000120652 7001_ $$00000-0002-0372-2266$$aPapillon-Cavanagh, Simon$$b13
000120652 7001_ $$aNikbakht, Hamid$$b14
000120652 7001_ $$aGayden, Tenzin$$b15
000120652 7001_ $$aTorchia, Jonathon$$b16
000120652 7001_ $$aPicard, Daniel$$b17
000120652 7001_ $$00000-0002-6173-6957$$aMerino, Diana M$$b18
000120652 7001_ $$aVladoiu, Maria$$b19
000120652 7001_ $$aLuu, Betty$$b20
000120652 7001_ $$aWu, Xiaochong$$b21
000120652 7001_ $$aDaniels, Craig$$b22
000120652 7001_ $$aHorswell, Stuart$$b23
000120652 7001_ $$aThompson, Yuan Yao$$b24
000120652 7001_ $$0P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc$$aHovestadt, Volker$$b25
000120652 7001_ $$0P:(DE-HGF)0$$aNorthcott, Paul A$$b26
000120652 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b27
000120652 7001_ $$aPeacock, John$$b28
000120652 7001_ $$00000-0001-6292-3087$$aWang, Xin$$b29
000120652 7001_ $$aMack, Stephen C$$b30
000120652 7001_ $$aReimand, Jüri$$b31
000120652 7001_ $$aAlbrecht, Steffen$$b32
000120652 7001_ $$aFontebasso, Adam M$$b33
000120652 7001_ $$aThiessen, Nina$$b34
000120652 7001_ $$aLi, Yisu$$b35
000120652 7001_ $$aSchein, Jacqueline E$$b36
000120652 7001_ $$aLee, Darlene$$b37
000120652 7001_ $$aCarlsen, Rebecca$$b38
000120652 7001_ $$aMayo, Michael$$b39
000120652 7001_ $$aTse, Kane$$b40
000120652 7001_ $$aTam, Angela$$b41
000120652 7001_ $$aDhalla, Noreen$$b42
000120652 7001_ $$aAlly, Adrian$$b43
000120652 7001_ $$aChuah, Eric$$b44
000120652 7001_ $$aCheng, Young$$b45
000120652 7001_ $$aPlettner, Patrick$$b46
000120652 7001_ $$aLi, Haiyan I$$b47
000120652 7001_ $$aCorbett, Richard D$$b48
000120652 7001_ $$aWong, Tina$$b49
000120652 7001_ $$aLong, William$$b50
000120652 7001_ $$aLoukides, James$$b51
000120652 7001_ $$aBuczkowicz, Pawel$$b52
000120652 7001_ $$aHawkins, Cynthia E$$b53
000120652 7001_ $$aTabori, Uri$$b54
000120652 7001_ $$aRood, Brian R$$b55
000120652 7001_ $$aMyseros, John S$$b56
000120652 7001_ $$aPacker, Roger J$$b57
000120652 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b58
000120652 7001_ $$0P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aLichter, Peter$$b59
000120652 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b60
000120652 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b61
000120652 7001_ $$aSchüller, Ulrich$$b62
000120652 7001_ $$aDirks, Peter$$b63
000120652 7001_ $$aHuang, Annie$$b64
000120652 7001_ $$aBouffet, Eric$$b65
000120652 7001_ $$aRutka, James T$$b66
000120652 7001_ $$00000-0003-0185-8861$$aBader, Gary D$$b67
000120652 7001_ $$aSwanton, Charles$$b68
000120652 7001_ $$aMa, Yusanne$$b69
000120652 7001_ $$aMoore, Richard A$$b70
000120652 7001_ $$00000-0002-0905-2742$$aMungall, Andrew J$$b71
000120652 7001_ $$aMajewski, Jacek$$b72
000120652 7001_ $$aJones, Steven J M$$b73
000120652 7001_ $$00000-0002-2146-4168$$aDas, Sunit$$b74
000120652 7001_ $$aMalkin, David$$b75
000120652 7001_ $$aJabado, Nada$$b76
000120652 7001_ $$aMarra, Marco A$$b77
000120652 7001_ $$aTaylor, Michael D$$b78
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