TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

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...

ver descrição completa

Detalhes bibliográficos
Autores: Remke M, Ramaswamy V, Peacock J, Shih DJ, Koelsche C, Northcott PA, Hill N, Cavalli FM, Kool M, Wang X, Mack SC, Barszczyk M, Morrissy AS, Wu X, Agnihotri S, Luu B, Jones DT, Garzia L, Dubuc AM, Zhukova N, Vanner R, Kros JM, French PJ, Van Meir EG, Vibhakar R, Zitterbart K, Chan JA, Bognár L, Klekner A, Lach B, Jung S, Saad AG, Liau LM, Albrecht S, Zollo M, Cooper MK, Thompson RC, Delattre OO, Bourdeaut F, Doz FF, Garami M, Hauser P, Carlotti CG, Van Meter TE, Massimi L, Fults D, Pomeroy SL, Kumabe T, Ra YS, Leonard JR, Elbabaa SK, Mora J, Rubin JB, Cho YJ, McLendon RE, Bigner DD, Eberhart CG, Fouladi M, Wechsler-Reya RJ, Faria CC, Croul SE, Huang A, Bouffet E, Hawkins CE, Dirks PB, Weiss WA, Schüller U, Pollack IF, Rutkowski S, Meyronet D, Jouvet A, Fèvre-Montange M, Jabado N, Perek-Polnik M, Grajkowska WA, Kim SK, Rutka JT, Malkin D, Tabori U, Pfister SM, Korshunov A, von Deimling A, Taylor MD
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Recursos:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p5170
Acesso em linha:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5170
Access Level:acceso abierto
Palavra-chave:TERT promoter mutations
SHH pathway
Adult
Medulloblastoma
Descrição
Resumo: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.

Registos relacionados