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Spatial heterogeneity in medulloblastoma

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 ; Peacock, John ; Wang, Xin ; Mack, Stephen C ; Reimand, Jüri ; Albrecht, Steffen ; Fontebasso, Adam M ; Thiessen, Nina ; Li, Yisu ; Schein, Jacqueline E ; Lee, Darlene ; Carlsen, Rebecca ; Mayo, Michael ; Tse, Kane ; Tam, Angela ; Dhalla, Noreen ; Ally, Adrian ; Chuah, Eric ; Cheng, Young ; Plettner, Patrick ; Li, Haiyan I ; Corbett, Richard D ; Wong, Tina ; Long, William ; Loukides, James ; Buczkowicz, Pawel ; Hawkins, Cynthia E ; Tabori, Uri ; Rood, Brian R ; Myseros, John S ; Packer, Roger J ; Korshunov, Andrey ; Lichter, Peter ; Kool, Marcel ; Pfister, Stefan M ; Schüller, Ulrich ; Dirks, Peter ; Huang, Annie ; Bouffet, Eric ; Rutka, James T ; Bader, Gary D ; Swanton, Charles ; Ma, Yusanne ; Moore, Richard A ; Mungall, Andrew J ; Majewski, Jacek ; Jones, Steven J M ; Das, Sunit ; Malkin, David ; Jabado, Nada ; Marra, Marco A ; Taylor, Michael D

Nature genetics, 2017-05, Vol.49 (5), p.780-788 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Spatial heterogeneity in medulloblastoma
Autor: 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 ; Peacock, John ; Wang, Xin ; Mack, Stephen C ; Reimand, Jüri ; Albrecht, Steffen ; Fontebasso, Adam M ; Thiessen, Nina ; Li, Yisu ; Schein, Jacqueline E ; Lee, Darlene ; Carlsen, Rebecca ; Mayo, Michael ; Tse, Kane ; Tam, Angela ; Dhalla, Noreen ; Ally, Adrian ; Chuah, Eric ; Cheng, Young ; Plettner, Patrick ; Li, Haiyan I ; Corbett, Richard D ; Wong, Tina ; Long, William ; Loukides, James ; Buczkowicz, Pawel ; Hawkins, Cynthia E ; Tabori, Uri ; Rood, Brian R ; Myseros, John S ; Packer, Roger J ; Korshunov, Andrey ; Lichter, Peter ; Kool, Marcel ; Pfister, Stefan M ; Schüller, Ulrich ; Dirks, Peter ; Huang, Annie ; Bouffet, Eric ; Rutka, James T ; Bader, Gary D ; Swanton, Charles ; Ma, Yusanne ; Moore, Richard A ; Mungall, Andrew J ; Majewski, Jacek ; Jones, Steven J M ; Das, Sunit ; Malkin, David ; Jabado, Nada ; Marra, Marco A ; Taylor, Michael D
Assuntos: Adult ; Aged ; Aged, 80 and over ; Biology ; Biomarkers ; Biopsy ; Brain ; Brain cancer ; Cerebellar Neoplasms - genetics ; Cerebellar Neoplasms - pathology ; Child ; Child, Preschool ; Children & youth ; Cluster Analysis ; Colleges & universities ; Consortia ; Diagnosis ; DNA Copy Number Variations ; Female ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Regulation, Neoplastic ; Gene mutations ; Genetic aspects ; Genetic Heterogeneity ; Genetic markers ; Genetics ; Genome-Wide Association Study ; Genomes ; Glioma ; Health aspects ; Hematology ; Heterogeneity ; Hospitals ; Humans ; Immunology ; INDEL Mutation ; Kidney cancer ; Laboratories ; Male ; Medical research ; Medulloblastoma ; Medulloblastoma - genetics ; Medulloblastoma - pathology ; Methods ; Middle Aged ; Mutation ; Neuropathology ; Neurosurgery ; Oncology ; Pediatrics ; Polymorphism, Single Nucleotide ; Principal Component Analysis ; Renal cell carcinoma ; Research centers ; Reverse Transcriptase Polymerase Chain Reaction ; Transcriptome ; Tumors
É parte de: Nature genetics, 2017-05, Vol.49 (5), p.780-788
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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These authors contributed equally.
Descrição: 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.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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Spatial heterogeneity in medulloblastoma

United States: Nature Publishing Group

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