000120652 001__ 120652 000120652 005__ 20240228145458.0 000120652 0247_ $$2doi$$a10.1038/ng.3838 000120652 0247_ $$2pmid$$apmid:28394352 000120652 0247_ $$2ISSN$$a1061-4036 000120652 0247_ $$2ISSN$$a1546-1718 000120652 0247_ $$2altmetric$$aaltmetric:18700090 000120652 037__ $$aDKFZ-2017-01079 000120652 041__ $$aeng 000120652 082__ $$a570 000120652 1001_ $$aMorrissy, A Sorana$$b0 000120652 245__ $$aSpatial heterogeneity in medulloblastoma. 000120652 260__ $$aNew York, NY$$bNature America$$c2017 000120652 3367_ $$2DRIVER$$aarticle 000120652 3367_ $$2DataCite$$aOutput Types/Journal article 000120652 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1533206386_14046 000120652 3367_ $$2BibTeX$$aARTICLE 000120652 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000120652 3367_ $$00$$2EndNote$$aJournal Article 000120652 520__ $$aSpatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor, which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation. 000120652 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0 000120652 588__ $$aDataset connected to CrossRef, PubMed, 000120652 7001_ $$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 000120652 773__ $$0PERI:(DE-600)1494946-5$$a10.1038/ng.3838$$gVol. 49, no. 5, p. 780 - 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