Journal Article

DKFZ-2017-01079

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Spatial heterogeneity in medulloblastoma.

Morrissy, A. S. ; Cavalli, F. M. G. ; Remke, M.DKFZ* ; Ramaswamy, V. ; Shih, D. J. H. ; Holgado, B. L. ; Farooq, H. ; Donovan, L. K. ; Garzia, L. ; Agnihotri, S. ; Kiehna, E. N. ; Mercier, E. ; Mayoh, C. ; Papillon-Cavanagh, S. ; Nikbakht, H. ; Gayden, T. ; Torchia, J. ; Picard, D. ; Merino, D. M. ; Vladoiu, M. ; Luu, B. ; Wu, X. ; Daniels, C. ; Horswell, S. ; Thompson, Y. Y. ; Hovestadt, V.DKFZ* ; Northcott, P. A.DKFZ* ; Jones, D.DKFZ* ; Peacock, J. ; Wang, X. ; Mack, S. C. ; Reimand, J. ; Albrecht, S. ; Fontebasso, A. M. ; Thiessen, N. ; Li, Y. ; Schein, J. E. ; Lee, D. ; Carlsen, R. ; Mayo, M. ; Tse, K. ; Tam, A. ; Dhalla, N. ; Ally, A. ; Chuah, E. ; Cheng, Y. ; Plettner, P. ; Li, H. I. ; Corbett, R. D. ; Wong, T. ; Long, W. ; Loukides, J. ; Buczkowicz, P. ; Hawkins, C. E. ; Tabori, U. ; Rood, B. R. ; Myseros, J. S. ; Packer, R. J. ; Korshunov, A.DKFZ* ; Lichter, P.DKFZ* ; Kool, M.DKFZ* ; Pfister, S.DKFZ* ; Schüller, U. ; Dirks, P. ; Huang, A. ; Bouffet, E. ; Rutka, J. T. ; Bader, G. D. ; Swanton, C. ; Ma, Y. ; Moore, R. A. ; Mungall, A. J. ; Majewski, J. ; Jones, S. J. M. ; Das, S. ; Malkin, D. ; Jabado, N. ; Marra, M. A. ; Taylor, M. D.

2017
Nature America New York, NY

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Please use a persistent id in citations: doi:10.1038/ng.3838

Abstract: Spatial 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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Contributing Institute(s):

1. Molekulare Genetik (B060)
2. Pädiatrische Neuroonkologie (B062)
3. KKE Neuropathologie (G380)
4. DKTK Essen (L401)
5. DKTK Heidelberg (L101)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2017

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 30 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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