Spatial heterogeneity in medulloblastoma
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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 B; 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.
in: NAT GENET, Jahrgang 49, Nr. 5, 05.2017, S. 780-788.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Spatial heterogeneity in medulloblastoma
AU - Morrissy, A Sorana
AU - Cavalli, Florence M G
AU - Remke, Marc
AU - Ramaswamy, Vijay
AU - Shih, David J H
AU - Holgado, Borja L
AU - Farooq, Hamza
AU - Donovan, Laura K
AU - Garzia, Livia
AU - Agnihotri, Sameer
AU - Kiehna, Erin N
AU - Mercier, Eloi
AU - Mayoh, Chelsea
AU - Papillon-Cavanagh, Simon
AU - Nikbakht, Hamid
AU - Gayden, Tenzin
AU - Torchia, Jonathon
AU - Picard, Daniel
AU - Merino, Diana M
AU - Vladoiu, Maria
AU - Luu, Betty
AU - Wu, Xiaochong
AU - Daniels, Craig
AU - Horswell, Stuart
AU - Thompson, Yuan Yao
AU - Hovestadt, Volker
AU - Northcott, Paul A
AU - Jones, David T W
AU - Peacock, John
AU - Wang, Xin
AU - Mack, Stephen C
AU - Reimand, Jüri
AU - Albrecht, Steffen
AU - Fontebasso, Adam M
AU - Thiessen, Nina
AU - Li, Yisu
AU - Schein, Jacqueline E
AU - Lee, Darlene
AU - Carlsen, Rebecca
AU - Mayo, Michael
AU - Tse, Kane
AU - Tam, Angela
AU - Dhalla, Noreen
AU - Ally, Adrian
AU - Chuah, Eric
AU - Cheng, Young
AU - Plettner, Patrick
AU - Li, Haiyan I
AU - Corbett, Richard D
AU - Wong, Tina
AU - Long, William
AU - Loukides, James
AU - Buczkowicz, Pawel
AU - Hawkins, Cynthia E
AU - Tabori, Uri
AU - Rood, Brian R
AU - Myseros, John S
AU - Packer, Roger J
AU - Korshunov, Andrey
AU - Lichter, Peter
AU - Kool, Marcel
AU - Pfister, Stefan M
AU - Schüller, Ulrich
AU - Dirks, Peter B
AU - Huang, Annie
AU - Bouffet, Eric
AU - Rutka, James T
AU - Bader, Gary D
AU - Swanton, Charles
AU - Ma, Yusanne
AU - Moore, Richard A
AU - Mungall, Andrew J
AU - Majewski, Jacek
AU - Jones, Steven J M
AU - Das, Sunit
AU - Malkin, David
AU - Jabado, Nada
AU - Marra, Marco A
AU - Taylor, Michael D
PY - 2017/5
Y1 - 2017/5
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/ng.3838
DO - 10.1038/ng.3838
M3 - SCORING: Journal article
C2 - 28394352
VL - 49
SP - 780
EP - 788
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 5
ER -