TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma
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- 作者：Marc Remke (1) (2) (3)
Vijay Ramaswamy (1) (2) (3)
John Peacock (1) (2) (3)
David J. H. Shih (1) (2) (3)
Christian Koelsche (4) (5)
Paul A. Northcott (6)
Nadia Hill (1) (2)
Florence M. G. Cavalli (1) (2)
Marcel Kool (6)
Xin Wang (1) (2) (3)
Stephen C. Mack (1) (2) (3)
Mark Barszczyk (1)
A. Sorana Morrissy (1) (2)
Xiaochong Wu (1) (2)
Sameer Agnihotri (1)
Betty Luu (1) (2)
David T. W. Jones (6)
Livia Garzia (1) (2)
Adrian M. Dubuc (1) (2) (3)
Nataliya Zhukova (1)
Robert Vanner (1)
Johan M. Kros (7)
Pim J. French (8)
Erwin G. Van Meir (9)
Rajeev Vibhakar (10)
Karel Zitterbart (11)
Jennifer A. Chan (12)
LzlBogn (13)
Almos Klekner (13)
Boleslaw Lach (14)
Shin Jung (15)
Ali G. Saad (16)
Linda M. Liau (17)
Steffen Albrecht (18)
Massimo Zollo (19) (20)
Michael K. Cooper (21)
Reid C. Thompson (22)
Oliver O. Delattre (23)
Franck Bourdeaut (23)
Franois F. Doz (24)
Mikl Garami (25)
Peter Hauser (25)
Carlos G. Carlotti (26)
Timothy E. Van Meter (27)
Luca Massimi (28)
Daniel Fults (29)
Scott L. Pomeroy (30)
Toshiro Kumabe (31)
Young Shin Ra (32)
Jeffrey R. Leonard (33)
Samer K. Elbabaa (34)
Jaume Mora (35)
Joshua B. Rubin (36)
Yoon-Jae Cho (57)
Roger E. McLendon (38)
Darell D. Bigner (38)
Charles G. Eberhart (39)
Maryam Fouladi (40)
Robert J. Wechsler-Reya (41)
Claudia C. Faria (42) (43)
Sidney E. Croul (3)
Annie Huang (44)
Eric Bouffet (44)
Cynthia E. Hawkins (45)
Peter B. Dirks (42)
William A. Weiss (37)
Ulrich Schler (46)
Ian F. Pollack (47)
Stefan Rutkowski (48)
David Meyronet (49) (56)
Anne Jouvet (49) (56)
Michelle Fre-Montange (50)
Nada Jabado (51)
Marta Perek-Polnik (52)
Wieslawa A. Grajkowska (53)
Seung-Ki Kim (54)
James T. Rutka (42)
David Malkin (44)
Uri Tabori (44)
Stefan M. Pfister (55) (6)
Andrey Korshunov (4) (5)
Andreas von Deimling (4) (5)
Michael D. Taylor (1) (2) (3) (42) - 关键词：TERT promoter mutations ; SHH pathway ; Adult ; Medulloblastoma
- 刊名：Acta Neuropathologica
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：126
- 期：6
- 页码：917-929
- 全文大小：
- 作者单位：Marc Remke (1) (2) (3)
Vijay Ramaswamy (1) (2) (3)
John Peacock (1) (2) (3)
David J. H. Shih (1) (2) (3)
Christian Koelsche (4) (5)
Paul A. Northcott (6)
Nadia Hill (1) (2)
Florence M. G. Cavalli (1) (2)
Marcel Kool (6)
Xin Wang (1) (2) (3)
Stephen C. Mack (1) (2) (3)
Mark Barszczyk (1)
A. Sorana Morrissy (1) (2)
Xiaochong Wu (1) (2)
Sameer Agnihotri (1)
Betty Luu (1) (2)
David T. W. Jones (6)
Livia Garzia (1) (2)
Adrian M. Dubuc (1) (2) (3)
Nataliya Zhukova (1)
Robert Vanner (1)
Johan M. Kros (7)
Pim J. French (8)
Erwin G. Van Meir (9)
Rajeev Vibhakar (10)
Karel Zitterbart (11)
Jennifer A. Chan (12)
LzlBogn (13)
Almos Klekner (13)
Boleslaw Lach (14)
Shin Jung (15)
Ali G. Saad (16)
Linda M. Liau (17)
Steffen Albrecht (18)
Massimo Zollo (19) (20)
Michael K. Cooper (21)
Reid C. Thompson (22)
Oliver O. Delattre (23)
Franck Bourdeaut (23)
Franois F. Doz (24)
Mikl Garami (25)
Peter Hauser (25)
Carlos G. Carlotti (26)
Timothy E. Van Meter (27)
Luca Massimi (28)
Daniel Fults (29)
Scott L. Pomeroy (30)
Toshiro Kumabe (31)
Young Shin Ra (32)
Jeffrey R. Leonard (33)
Samer K. Elbabaa (34)
Jaume Mora (35)
Joshua B. Rubin (36)
Yoon-Jae Cho (57)
Roger E. McLendon (38)
Darell D. Bigner (38)
Charles G. Eberhart (39)
Maryam Fouladi (40)
Robert J. Wechsler-Reya (41)
Claudia C. Faria (42) (43)
Sidney E. Croul (3)
Annie Huang (44)
Eric Bouffet (44)
Cynthia E. Hawkins (45)
Peter B. Dirks (42)
William A. Weiss (37)
Ulrich Schler (46)
Ian F. Pollack (47)
Stefan Rutkowski (48)
David Meyronet (49) (56)
Anne Jouvet (49) (56)
Michelle Fre-Montange (50)
Nada Jabado (51)
Marta Perek-Polnik (52)
Wieslawa A. Grajkowska (53)
Seung-Ki Kim (54)
James T. Rutka (42)
David Malkin (44)
Uri Tabori (44)
Stefan M. Pfister (55) (6)
Andrey Korshunov (4) (5)
Andreas von Deimling (4) (5)
Michael D. Taylor (1) (2) (3) (42)
1. The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada
2. Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada
3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
4. Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany
5. Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany
6. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
7. Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands
8. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
9. Departments of Neurosurgery and Hematology and Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, USA
10. Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA
11. Department of Pediatric Oncology, School of Medicine, Masaryk University and University Hospital Brno, Brno, Czech Republic
12. Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada
13. Department of Neurosurgery, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary
14. Division of Anatomical Pathology, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
15. Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Chonnam, South Korea
16. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
17. Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
18. Department of Pathology, McGill University, Montreal, QC, Canada
19. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University of Naples, Naples, Italy
20. CEINGE Biotecnologie Avanzate, Naples, Italy
21. Department of Neurology, Vanderbilt Medical Center, Nashville, TN, USA
22. Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN, USA
23. Laboratoire de Gique et Biologie des Cancers, Institut Curie, Paris, France
24. Department of Pediatric Oncology, Institut Curie and University Paris Descartes, Sorbonne Paris Cit Paris, France
25. 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
26. Department of Surgery and Anatomy, Faculty of Medicine of Ribeiro Preto, Universidade de So Paulo, So Paulo, Brazil
27. Pediatric Hematology-Oncology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
28. Pediatric Neurosurgery, Catholic University Medical School, Rome, Italy
29. Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, USA
30. Department of Neurology, Harvard Medical School, Children Hospital Boston, Boston, ME, USA
31. Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan
32. Department of Neurosurgery, Asan Medical Center, University of Ulsan, Seoul, South Korea
33. Division of Pediatric Neurosurgery, Department of Neurosurgery, Washington University School of Medicine, St. Louis Children Hospital, St. Louis, MO, USA
34. Division of Pediatric Neurosurgery, Department of Neurological Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA
35. Developmental Tumor Biology Laboratory, Hospital Sant Joan de D, Barcelona, Spain
36. Departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine, St. Louis Children Hospital, St. Louis, MO, USA
57. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA
38. Department of Pathology, Duke University, Durham, NC, USA
39. Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore, MD, USA
40. Division of Oncology, Cincinnati Children Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA
41. Sanford-Burnham Medical Research Institute, La Jolla, CA, USA
42. Division of Neurosurgery, Department of Surgery, The Hospital for Sick Children and The Arthur and Sonia Labatt Brain Tumour Research Centre, Toronto, ON, Canada
43. Division of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte EPE, Lisbon, Portugal
44. Division of Haematology and Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
45. Department of Pathology, The Hospital for Sick Children, Toronto, ON, Canada
37. Department of Neurology, University of California, San Francisco, San Francisco, CA, USA
46. Center for Neuropathology and Prion Research, University of Munich, Munich, Germany
47. Department of Neurological Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
48. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
49. Neuro-oncology and Neuro-inflammation Team, Inserm U1028, CNRS UMR 5292, Neuroscience Center, University Lyon 1, 69000, Lyon, France
56. Hospices Civils de Lyon, Centre de Pathologie et de Neuropathologie Est, Lyon, 69003, France
50. Centre de Recherche en Neurosciences, INSERM U1028, CNRS UMR5292, Universitde Lyon, Lyon, France
51. Division of Experimental Medicine, McGill University, Montreal, QC, Canada
52. Department of Oncology, The Children Memorial Health Institute, Warsaw, Poland
53. Department of Pathology, The Children Memorial Health Institute, Warsaw, Poland
54. Division of Pediatric Neurosurgery, Department of Neurosurgery, Seoul National University Children Hospital, Seoul, Korea
55. Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany - ISSN：1432-0533
文摘
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.