File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

TitleTERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma
Authors
KeywordsAdult
Medulloblastoma
SHH pathway
TERT promoter mutations
Issue Date2013
Citation
Acta Neuropathologica, 2013, v. 126, n. 6, p. 917-929 How to Cite?
AbstractTelomerase 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. © Springer-Verlag Berlin Heidelberg 2013.
Persistent Identifierhttp://hdl.handle.net/10722/313990
ISSN
2023 Impact Factor: 9.3
2023 SCImago Journal Rankings: 4.720
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRemke, Marc-
dc.contributor.authorRamaswamy, Vijay-
dc.contributor.authorPeacock, John-
dc.contributor.authorShih, David J.H.-
dc.contributor.authorKoelsche, Christian-
dc.contributor.authorNorthcott, Paul A.-
dc.contributor.authorHill, Nadia-
dc.contributor.authorCavalli, Florence M.G.-
dc.contributor.authorKool, Marcel-
dc.contributor.authorWang, Xin-
dc.contributor.authorMack, Stephen C.-
dc.contributor.authorBarszczyk, Mark-
dc.contributor.authorMorrissy, A. Sorana-
dc.contributor.authorWu, Xiaochong-
dc.contributor.authorAgnihotri, Sameer-
dc.contributor.authorLuu, Betty-
dc.contributor.authorJones, David T.W.-
dc.contributor.authorGarzia, Livia-
dc.contributor.authorDubuc, Adrian M.-
dc.contributor.authorZhukova, Nataliya-
dc.contributor.authorVanner, Robert-
dc.contributor.authorKros, Johan M.-
dc.contributor.authorFrench, Pim J.-
dc.contributor.authorVan Meir, Erwin G.-
dc.contributor.authorVibhakar, Rajeev-
dc.contributor.authorZitterbart, Karel-
dc.contributor.authorChan, Jennifer A.-
dc.contributor.authorBognár, László-
dc.contributor.authorKlekner, Almos-
dc.contributor.authorLach, Boleslaw-
dc.contributor.authorJung, Shin-
dc.contributor.authorSaad, Ali G.-
dc.contributor.authorLiau, Linda M.-
dc.contributor.authorAlbrecht, Steffen-
dc.contributor.authorZollo, Massimo-
dc.contributor.authorCooper, Michael K.-
dc.contributor.authorThompson, Reid C.-
dc.contributor.authorDelattre, Oliver O.-
dc.contributor.authorBourdeaut, Franck-
dc.contributor.authorDoz, François F.-
dc.contributor.authorGarami, Miklós-
dc.contributor.authorHauser, Peter-
dc.contributor.authorCarlotti, Carlos G.-
dc.contributor.authorVan Meter, Timothy E.-
dc.contributor.authorMassimi, Luca-
dc.contributor.authorFults, Daniel-
dc.contributor.authorPomeroy, Scott L.-
dc.contributor.authorKumabe, Toshiro-
dc.contributor.authorRa, Young Shin-
dc.contributor.authorLeonard, Jeffrey R.-
dc.contributor.authorElbabaa, Samer K.-
dc.contributor.authorMora, Jaume-
dc.contributor.authorRubin, Joshua B.-
dc.contributor.authorCho, Yoon Jae-
dc.contributor.authorMcLendon, Roger E.-
dc.contributor.authorBigner, Darell D.-
dc.contributor.authorEberhart, Charles G.-
dc.contributor.authorFouladi, Maryam-
dc.contributor.authorWechsler-Reya, Robert J.-
dc.contributor.authorFaria, Claudia C.-
dc.contributor.authorCroul, Sidney E.-
dc.contributor.authorHuang, Annie-
dc.contributor.authorBouffet, Eric-
dc.contributor.authorHawkins, Cynthia E.-
dc.contributor.authorDirks, Peter B.-
dc.contributor.authorWeiss, William A.-
dc.contributor.authorSchüller, Ulrich-
dc.contributor.authorPollack, Ian F.-
dc.contributor.authorRutkowski, Stefan-
dc.contributor.authorMeyronet, David-
dc.contributor.authorJouvet, Anne-
dc.contributor.authorFèvre-Montange, Michelle-
dc.contributor.authorJabado, Nada-
dc.contributor.authorPerek-Polnik, Marta-
dc.contributor.authorGrajkowska, Wieslawa A.-
dc.contributor.authorKim, Seung Ki-
dc.contributor.authorRutka, James T.-
dc.contributor.authorMalkin, David-
dc.contributor.authorTabori, Uri-
dc.contributor.authorPfister, Stefan M.-
dc.contributor.authorKorshunov, Andrey-
dc.contributor.authorVon Deimling, Andreas-
dc.contributor.authorTaylor, Michael D.-
dc.date.accessioned2022-07-06T11:28:45Z-
dc.date.available2022-07-06T11:28:45Z-
dc.date.issued2013-
dc.identifier.citationActa Neuropathologica, 2013, v. 126, n. 6, p. 917-929-
dc.identifier.issn0001-6322-
dc.identifier.urihttp://hdl.handle.net/10722/313990-
dc.description.abstractTelomerase 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. © Springer-Verlag Berlin Heidelberg 2013.-
dc.languageeng-
dc.relation.ispartofActa Neuropathologica-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAdult-
dc.subjectMedulloblastoma-
dc.subjectSHH pathway-
dc.subjectTERT promoter mutations-
dc.titleTERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1007/s00401-013-1198-2-
dc.identifier.pmid24174164-
dc.identifier.pmcidPMC3830749-
dc.identifier.scopuseid_2-s2.0-84892621211-
dc.identifier.volume126-
dc.identifier.issue6-
dc.identifier.spage917-
dc.identifier.epage929-
dc.identifier.eissn1432-0533-
dc.identifier.isiWOS:000327100500011-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats