TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma
Standard
TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma. / 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; Pomeroy, Scott L; 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.
In: ACTA NEUROPATHOL, Vol. 126, No. 6, 01.12.2013, p. 917-29.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma
AU - Remke, Marc
AU - Ramaswamy, Vijay
AU - Peacock, John
AU - Shih, David J H
AU - Koelsche, Christian
AU - Northcott, Paul A
AU - Hill, Nadia
AU - Cavalli, Florence M G
AU - Kool, Marcel
AU - Wang, Xin
AU - Mack, Stephen C
AU - Barszczyk, Mark
AU - Morrissy, A Sorana
AU - Wu, Xiaochong
AU - Agnihotri, Sameer
AU - Luu, Betty
AU - Jones, David T W
AU - Garzia, Livia
AU - Dubuc, Adrian M
AU - Zhukova, Nataliya
AU - Vanner, Robert
AU - Kros, Johan M
AU - French, Pim J
AU - Van Meir, Erwin G
AU - Vibhakar, Rajeev
AU - Zitterbart, Karel
AU - Chan, Jennifer A
AU - Bognár, László
AU - Klekner, Almos
AU - Lach, Boleslaw
AU - Jung, Shin
AU - Saad, Ali G
AU - Liau, Linda M
AU - Albrecht, Steffen
AU - Zollo, Massimo
AU - Cooper, Michael K
AU - Thompson, Reid C
AU - Delattre, Oliver O
AU - Bourdeaut, Franck
AU - Doz, François F
AU - Garami, Miklós
AU - Hauser, Peter
AU - Carlotti, Carlos G
AU - Van Meter, Timothy E
AU - Massimi, Luca
AU - Fults, Daniel
AU - Pomeroy, Scott L
AU - Kumabe, Toshiro
AU - Ra, Young Shin
AU - Leonard, Jeffrey R
AU - Elbabaa, Samer K
AU - Mora, Jaume
AU - Rubin, Joshua B
AU - Cho, Yoon-Jae
AU - McLendon, Roger E
AU - Bigner, Darell D
AU - Eberhart, Charles G
AU - Fouladi, Maryam
AU - Wechsler-Reya, Robert J
AU - Faria, Claudia C
AU - Croul, Sidney E
AU - Huang, Annie
AU - Bouffet, Eric
AU - Hawkins, Cynthia E
AU - Dirks, Peter B
AU - Weiss, William A
AU - Schüller, Ulrich
AU - Pollack, Ian F
AU - Rutkowski, Stefan
AU - Meyronet, David
AU - Jouvet, Anne
AU - Fèvre-Montange, Michelle
AU - Jabado, Nada
AU - Perek-Polnik, Marta
AU - Grajkowska, Wieslawa A
AU - Kim, Seung-Ki
AU - Rutka, James T
AU - Malkin, David
AU - Tabori, Uri
AU - Pfister, Stefan M
AU - Korshunov, Andrey
AU - von Deimling, Andreas
AU - Taylor, Michael D
PY - 2013/12/1
Y1 - 2013/12/1
N2 - 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.
AB - 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.
U2 - 10.1007/s00401-013-1198-2
DO - 10.1007/s00401-013-1198-2
M3 - SCORING: Journal article
C2 - 24174164
VL - 126
SP - 917
EP - 929
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 6
ER -