TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma
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Author
Remke, Marc
Ramaswamy, Vijay
Peacock, John
Shih, David J. H.
Koelsche, Christian
Northcott, Paul A.
Hill, Nadia
Cavalli, Florence M. G.
Kool, Marcel
Wang, Xin
Mack, Stephen C.
Barszczyk, Mark
Morrissy, A. Sorana
Wu, Xiaochong
Agnihotri, Sameer
Luu, Betty
Jones, David T. W.
Garzia, Livia
Dubuc, Adrian M.
Zhukova, Nataliya
Vanner, Robert
Kros, Johan M.
French, Pim J.
Van Meir, Erwin G.
Vibhakar, Rajeev
Zitterbart, Karel
Chan, Jennifer A.
Bognár, László
Klekner, Almos
Lach, Boleslaw
Jung, Shin
Saad, Ali G.
Liau, Linda M.
Albrecht, Steffen
Zollo, Massimo
Cooper, Michael K.
Thompson, Reid C.
Delattre, Oliver O.
Bourdeaut, Franck
Doz, François F.
Garami, Miklós
Hauser, Peter
Carlotti, Carlos G.
Van Meter, Timothy E.
Massimi, Luca
Fults, Daniel
Kumabe, Toshiro
Ra, Young Shin
Leonard, Jeffrey R.
Elbabaa, Samer K.
Mora, Jaume
Rubin, Joshua B.
Cho, Yoon-Jae
McLendon, Roger E.
Bigner, Darell D.
Eberhart, Charles G.
Fouladi, Maryam
Wechsler-Reya, Robert J.
Faria, Claudia C.
Croul, Sidney E.
Huang, Annie
Bouffet, Eric
Hawkins, Cynthia E.
Dirks, Peter B.
Weiss, William A.
Schüller, Ulrich
Pollack, Ian F.
Rutkowski, Stefan
Meyronet, David
Jouvet, Anne
Fèvre-Montange, Michelle
Jabado, Nada
Perek-Polnik, Marta
Grajkowska, Wieslawa A.
Kim, Seung-Ki
Rutka, James T.
Malkin, David
Tabori, Uri
Pfister, Stefan M.
Korshunov, Andrey
von Deimling, Andreas
Taylor, Michael D.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1007/s00401-013-1198-2Metadata
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Remke, M., V. Ramaswamy, J. Peacock, D. J. H. Shih, C. Koelsche, P. A. Northcott, N. Hill, et al. 2013. “TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.” Acta Neuropathologica 126 (1): 917-929. doi:10.1007/s00401-013-1198-2. http://dx.doi.org/10.1007/s00401-013-1198-2.Abstract
Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association with increased patient age. The prognostic implications of these mutations were highly subgroup-specific. TERT mutations identified a subset with good and poor prognosis in SHH and Group 4 tumors, respectively. Monosomy 6 was mostly restricted to WNT tumors without TERT mutations. Hallmark SHH focal copy number aberrations and chromosome 10q deletion were mutually exclusive with TERT mutations within SHH tumors. TERT promoter mutations are the most common recurrent somatic point mutation in medulloblastoma, and are very highly enriched in adult SHH and WNT tumors. TERT mutations define a subset of SHH medulloblastoma with distinct demographics, cytogenetics, and outcomes. Electronic supplementary material The online version of this article (doi:10.1007/s00401-013-1198-2) contains supplementary material, which is available to authorized users.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830749/pdf/Terms of Use
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