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TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.

Publication ,  Journal Article
Remke, M; Ramaswamy, V; Peacock, J; Shih, DJH; Koelsche, C; Northcott, PA; Hill, N; Cavalli, FMG; Kool, M; Wang, X; Mack, SC; Barszczyk, M ...
Published in: Acta Neuropathol
December 2013

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.

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Published In

Acta Neuropathol

DOI

EISSN

1432-0533

Publication Date

December 2013

Volume

126

Issue

6

Start / End Page

917 / 929

Location

Germany

Related Subject Headings

  • Telomerase
  • Promoter Regions, Genetic
  • Prognosis
  • Neurology & Neurosurgery
  • Mutation
  • Middle Aged
  • Medulloblastoma
  • Male
  • Infant
  • Humans
 

Citation

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Remke, M., Ramaswamy, V., Peacock, J., Shih, D. J. H., Koelsche, C., Northcott, P. A., … Taylor, M. D. (2013). TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma. Acta Neuropathol, 126(6), 917–929. https://doi.org/10.1007/s00401-013-1198-2
Remke, Marc, Vijay Ramaswamy, John Peacock, David J. H. Shih, Christian Koelsche, Paul A. Northcott, Nadia Hill, et al. “TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.Acta Neuropathol 126, no. 6 (December 2013): 917–29. https://doi.org/10.1007/s00401-013-1198-2.
Remke M, Ramaswamy V, Peacock J, Shih DJH, Koelsche C, Northcott PA, et al. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma. Acta Neuropathol. 2013 Dec;126(6):917–29.
Remke, Marc, et al. “TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.Acta Neuropathol, vol. 126, no. 6, Dec. 2013, pp. 917–29. Pubmed, doi:10.1007/s00401-013-1198-2.
Remke M, Ramaswamy V, Peacock J, Shih DJH, Koelsche C, Northcott PA, Hill N, Cavalli FMG, Kool M, Wang X, Mack SC, Barszczyk M, Morrissy AS, Wu X, Agnihotri S, Luu B, Jones DTW, 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 Y-J, 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 S-K, Rutka JT, Malkin D, Tabori U, Pfister SM, Korshunov A, von Deimling A, Taylor MD. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma. Acta Neuropathol. 2013 Dec;126(6):917–929.
Journal cover image

Published In

Acta Neuropathol

DOI

EISSN

1432-0533

Publication Date

December 2013

Volume

126

Issue

6

Start / End Page

917 / 929

Location

Germany

Related Subject Headings

  • Telomerase
  • Promoter Regions, Genetic
  • Prognosis
  • Neurology & Neurosurgery
  • Mutation
  • Middle Aged
  • Medulloblastoma
  • Male
  • Infant
  • Humans