Spatial heterogeneity in medulloblastoma

作者：Morrissy A Sorana; Cavalli Florence M G; Remke Marc; Ramaswamy Vijay; Shih David J H; Holgado Borja L; Farooq Hamza; Donovan Laura K; Garzia Livia; Agnihotri Sameer; Kiehna Erin N; Mercier Eloi; Mayoh Chelsea; Papillon Cavanagh Simon; Nikbakht Hamid; Gayden Tenzin; Torchia Jonathon; Picard Daniel; Merino Diana M; Vladoiu Maria; Luu Betty; Wu Xiaochong; Daniels Craig; Horswell Stuart; Thompson Yuan Yao; Hovestadt Volker; Northcott Paul A; Jones David T W

来源：Nature Genetics, 2017, 49(5): 780-+.

DOI：10.1038/ng.3838

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.

• 出版日期2017-5