Remke, Marc and Ramaswamy, Vijay and Peacock, John and Shih, David J. H. and Koelsche, Christian and Bognár, László and Klekner, Álmos and Garami, Miklós and Hauser, Péter (2013) TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma. Acta Neuropathologica, 126 (6). pp. 917-929. ISSN 0001-6322
![[img]](http://real.mtak.hu/style/images/fileicons/text.png) |
Text
TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.pdf Restricted to Registered users only Download (818kB) | Request a copy |
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.
| Item Type: | Article |
|---|---|
| Additional Information: | Teljes szerzőség: Remke, Marc és Ramaswamy, Vijay és Peacock, John és Shih, David J. H. és Koelsche, Christian és Northcott, Paul A. és Hill, Nadia és Cavalli, Florence M. G. és Kool, Marcel és Wang, Xin és Mack, Stephen C. és Barszczyk, Mark és Morrissy, A. Sorana és Wu, Xiaochong és Agnihotri, Sameer és Luu, Betty és Jones, David T. W. és Garzia, Livia és Dubuc, Adrian M. és Zhukova, Nataliya és Vanner, Robert és Kros, Johan M. és French, Pim J. és Van Meir, Erwin G. és Vibhakar, Rajeev és Zitterbart, Karel és Chan, Jennifer A. és Bognár, László és Klekner, Almos és Lach, Boleslaw és Jung, Shin és Saad, Ali G. és Liau, Linda M. és Albrecht, Steffen és Zollo, Massimo és Cooper, Michael K. és Thompson, Reid C. és Delattre, Oliver O. és Bourdeaut, Franck és Doz, François F. és Garami, Miklós és Hauser, Peter és Carlotti, Carlos G. és Van Meter, Timothy E. és Massimi, Luca és Fults, Daniel és Pomeroy, Scott L. és Kumabe, Toshiro és Ra, Young Shin és Leonard, Jeffrey R. és Elbabaa, Samer K. és Mora, Jaume és Rubin, Joshua B. és Cho, Yoon-Jae és McLendon, Roger E. és Bigner, Darell D. és Eberhart, Charles G. és Fouladi, Maryam és Wechsler-Reya, Robert J. és Faria, Claudia C. és Croul, Sidney E. és Huang, Annie és Bouffet, Eric és Hawkins, Cynthia E. és Dirks, Peter B. és Weiss, William A. és Schüller, Ulrich és Pollack, Ian F. és Rutkowski, Stefan és Meyronet, David és Jouvet, Anne és Fèvre-Montange, Michelle és Jabado, Nada és Perek-Polnik, Marta és Grajkowska, Wieslawa A. és Kim, Seung-Ki és Rutka, James T. és Malkin, David és Tabori, Uri és Pfister, Stefan M. és Korshunov, Andrey és von Deimling, Andreas és Taylor, Michael D. |
| Uncontrolled Keywords: | TERT promoter mutations, SHH pathway, Adult, Medulloblastoma |
| Subjects: | R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia |
| Depositing User: | Dr. Álmos Klekner |
| Date Deposited: | 26 Sep 2014 18:02 |
| Last Modified: | 26 Sep 2014 18:02 |
| URI: | http://real.mtak.hu/id/eprint/15349 |
Actions (login required)
 |
Edit Item |
