Spatial heterogeneity in medulloblastomaMore about Open Access at the Crick
Authors listA Sorana Morrissy Florence MG Cavalli Marc Remke Vijay Ramaswamy David JH Shih Borja L Holgado Hamza Farooq Laura K Donovan Livia Garzia Sameer Agnihotri Erin N Kiehna Eloi Mercier Chelsea Mayoh Simon Papillon-Cavanagh Hamid Nikbakht Tenzin Gayden Jonathon Torchia Daniel Picard Diana M Merino Maria Vladoiu Betty Luu Xiaochong Wu Craig Daniels Stuart Horswell Yuan Yao Thompson Volker Hovestadt Paul A Northcott David TW Jones John Peacock Xin Wang Stephen C Mack Jüri Reimand Steffen Albrecht Adam M Fontebasso Nina Thiessen Yisu Li Jacqueline E Schein Darlene Lee Rebecca Carlsen Michael Mayo Kane Tse Angela Tam Noreen Dhalla Adrian Ally Eric Chuah Young Cheng Patrick Plettner Haiyan I Li Richard D Corbett Tina Wong William Long James Loukides Pawel Buczkowicz Cynthia E Hawkins Uri Tabori Brian R Rood John S Myseros Roger J Packer Andrey Korshunov Peter Lichter Marcel Kool Stefan M Pfister Ulrich Schüller Peter Dirks Annie Huang Eric Bouffet James T Rutka Gary D Bader Charles Swanton Yusanne Ma Richard A Moore Andrew J Mungall Jacek Majewski Steven JM Jones Sunit Das David Malkin Nada Jabado Marco A Marra Michael D Taylor
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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.
Journal Nature Genetics
Issue number 5