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Germ-line and somatic DICER1 mutations in pineoblastoma

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Abstract

Germ-line RB-1 mutations predispose to pineoblastoma (PinB), but other predisposing genetic factors are not well established. We recently identified a germ-line DICER1 mutation in a child with a PinB. This was accompanied by loss of heterozygosity (LOH) of the wild-type allele within the tumour. We set out to establish the prevalence of DICER1 mutations in an opportunistically ascertained series of PinBs. Twenty-one PinB cases were studied: Eighteen cases had not undergone previous testing for DICER1 mutations; three patients were known carriers of germ-line DICER1 mutations. The eighteen PinBs were sequenced by Sanger and/or Fluidigm-based next-generation sequencing to identify DICER1 mutations in blood gDNA and/or tumour gDNA. Testing for somatic DICER1 mutations was also conducted on one case with a known germ-line DICER1 mutation. From the eighteen PinBs, we identified four deleterious DICER1 mutations, three of which were germ line in origin, and one for which a germ line versus somatic origin could not be determined; in all four, the second allele was also inactivated leading to complete loss of DICER1 protein. No somatic DICER1 RNase IIIb mutations were identified. One PinB arising in a germ-line DICER1 mutation carrier was found to have LOH. This study suggests that germ-line DICER1 mutations make a clinically significant contribution to PinB, establishing DICER1 as an important susceptibility gene for PinB and demonstrates PinB to be a manifestation of a germ-line DICER1 mutation. The means by which the second allele is inactivated may differ from other DICER1-related tumours.

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References

  1. Anglesio MS, Wang Y, Yang W, Senz J, Wan A, Heravi-Moussavi A, Salamanca C, Maines-Bandiera S, Huntsman DG, Morin GB (2013) Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse-strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage. J Pathol 229(3):400–409. doi:10.1002/path.4135

    Article  PubMed  CAS  Google Scholar 

  2. Bahubeshi A, Bal N, Rio Frio T, Hamel N, Pouchet C, Yilmaz A, Bouron-Dal Soglio D, Williams GM, Tischkowitz M, Priest JR, Foulkes WD (2010) Germline DICER1 mutations and familial cystic nephroma. J Med Genet 47(12):863–866. doi:10.1136/jmg.2010.081216

    Article  PubMed  Google Scholar 

  3. Bahubeshi A, Tischkowitz M, Foulkes WD (2011) miRNA processing and human cancer: DICER1 cuts the mustard. Sci Transl Med 3(111):111ps146. doi:10.1126/scitranslmed.3002493

    Article  Google Scholar 

  4. Blach LE, McCormick B, Abramson DH, Ellsworth RM (1994) Trilateral retinoblastoma–incidence and outcome: a decade of experience. Int J Radiat Oncol Biol Phys 29(4):729–733

    Article  PubMed  CAS  Google Scholar 

  5. Cross SF, Arbuckle S, Priest JR, Marshall G, Charles A, Dalla Pozza L (2010) Familial pleuropulmonary blastoma in Australia. Pediatr Blood Cancer 55(7):1417–1419. doi:10.1002/pbc.22592

    Article  PubMed  Google Scholar 

  6. Damiani D, Alexander JJ, O’Rourke JR, McManus M, Jadhav AP, Cepko CL, Hauswirth WW, Harfe BD, Strettoi E (2008) Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J Neurosci 28(19):4878–4887. doi:10.1523/JNEUROSCI.0828-08.2008

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. de Kock L, Plourde F, Carter MT, Hamel N, Srivastava A, Meyn MS, Arseneau J, Soglio DB, Foulkes WD (2013) Germ-line and somatic DICER1 mutations in a pleuropulmonary blastoma. Pediatr Blood Cancer 60(12):2091–2092. doi:10.1002/pbc.24692

    PubMed  Google Scholar 

  8. de Kock L, Sabbaghian N, Plourde F, Srivastava A, Weber E, Bouron-Dal Soglio D, Hamel N, Choi JH, Park SH, Deal CL, Kelsey MM, Dishop MK, Esbenshade A, Kuttesch JF, Jacques TS, Perry A, Leichter H, Maeder P, Brundler MA, Warner J, Neal J, Zacharin M, Korbonits M, Cole T, Traunecker H, McLean TW, Rotondo F, Lepage P, Albrecht S, Horvath E, Kovacs K, Priest JR, Foulkes WD (2014) Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. Acta Neuropathol. doi:10.1007/s00401-014-1285-z

    PubMed Central  Google Scholar 

  9. de Kock L, Sabbaghian N, Soglio DB, Guillerman RP, Park BK, Chami R, Deal CL, Priest JR, Foulkes WD (2014) Exploring the association between DICER1 mutations and differentiated thyroid carcinoma. J Clin Endocrinol Metab. doi:10.1210/jc.2013-4206

    PubMed  Google Scholar 

  10. Doros L, Yang J, Dehner L, Rossi CT, Skiver K, Jarzembowski JA, Messinger Y, Schultz KA, Williams G, Andre N, Hill DA (2012) DICER1 mutations in embryonal rhabdomyosarcomas from children with and without familial PPB-tumor predisposition syndrome. Pediatr Blood Cancer 59(3):558–560. doi:10.1002/pbc.24020

    Article  PubMed  PubMed Central  Google Scholar 

  11. Doros LA, Rossi CT, Yang J, Field A, Williams GM, Messinger Y, Cajaiba MM, Perlman EJ, A Schultz K, Cathro HP, Legallo RD, Lafortune KA, Chikwava KR, Faria P, Geller JI, Dome JS, Mullen EA, Gratias EJ, Dehner LP, Hill DA (2014) DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma. Mod Pathol. doi:10.1038/modpathol.2013.242

    PubMed  Google Scholar 

  12. Fauchon F, Jouvet A, Paquis P, Saint-Pierre G, Mottolese C, Ben Hassel M, Chauveinc L, Sichez JP, Philippon J, Schlienger M, Bouffet E (2000) Parenchymal pineal tumors: a clinicopathological study of 76 cases. Int J Radiat Oncol Biol Phys 46(4):959–968

    Article  PubMed  CAS  Google Scholar 

  13. Foulkes WD, Bahubeshi A, Hamel N, Pasini B, Asioli S, Baynam G, Choong CS, Charles A, Frieder RP, Dishop MK, Graf N, Ekim M, Bouron-Dal Soglio D, Arseneau J, Young RH, Sabbaghian N, Srivastava A, Tischkowitz MD, Priest JR (2011) Extending the phenotypes associated with DICER1 mutations. Hum Mutat 32(12):1381–1384. doi:10.1002/humu.21600

    Article  PubMed  CAS  Google Scholar 

  14. Gurtan AM, Lu V, Bhutkar A, Sharp PA (2012) In vivo structure-function analysis of human Dicer reveals directional processing of precursor miRNAs. RNA 18(6):1116–1122. doi:10.1261/rna.032680.112

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Heravi-Moussavi A, Anglesio MS, Cheng SW, Senz J, Yang W, Prentice L, Fejes AP, Chow C, Tone A, Kalloger SE, Hamel N, Roth A, Ha G, Wan AN, Maines-Bandiera S, Salamanca C, Pasini B, Clarke BA, Lee AF, Lee CH, Zhao C, Young RH, Aparicio SA, Sorensen PH, Woo MM, Boyd N, Jones SJ, Hirst M, Marra MA, Gilks B, Shah SP, Foulkes WD, Morin GB, Huntsman DG (2012) Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med 366(3):234–242. doi:10.1056/NEJMoa1102903

    Article  PubMed  CAS  Google Scholar 

  16. Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ (2009) DICER1 mutations in familial pleuropulmonary blastoma. Science 325(5943):965. doi:10.1126/science.1174334

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Karaca E, Weitzer S, Pehlivan D, Shiraishi H, Gogakos T, Hanada T, Jhangiani SN, Wiszniewski W, Withers M, Campbell IM, Erdin S, Isikay S, Franco LM, Gonzaga-Jauregui C, Gambin T, Gelowani V, Hunter JV, Yesil G, Koparir E, Yilmaz S, Brown M, Briskin D, Hafner M, Morozov P, Farazi TA, Bernreuther C, Glatzel M, Trattnig S, Friske J, Kronnerwetter C, Bainbridge MN, Gezdirici A, Seven M, Muzny DM, Boerwinkle E, Ozen M, Clausen T, Tuschl T, Yuksel A, Hess A, Gibbs RA, Martinez J, Penninger JM, Lupski JR (2014) Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function. Cell 157(3):636–650. doi:10.1016/j.cell.2014.02.058

    Article  PubMed  CAS  Google Scholar 

  18. Kees UR, Biegel JA, Ford J, Ranford PR, Peroni SE, Hallam LA, Parmiter AH, Willoughby ML, Spagnolo D (1994) Enhanced MYCN expression and isochromosome 17q in pineoblastoma cell lines. Genes Chromosomes Cancer 9(2):129–135

    Article  PubMed  CAS  Google Scholar 

  19. Kees UR, Spagnolo D, Hallam LA, Ford J, Ranford PR, Baker DL, Callen DF, Biegel JA (1998) A new pineoblastoma cell line, PER-480, with der(10)t(10;17), der(16)t(1;16), and enhanced MYC expression in the absence of gene amplification. Cancer Genet Cytogenet 100(2):159–164

    Article  PubMed  CAS  Google Scholar 

  20. Kivela T (1999) Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma. J Clin Oncol 17(6):1829–1837

    PubMed  CAS  Google Scholar 

  21. Kumar MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, Kirsch DG, Golub TR, Jacks T (2009) Dicer1 functions as a haploinsufficient tumor suppressor. Genes Dev 23(23):2700–2704. doi:10.1101/gad.1848209

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Lambertz I, Nittner D, Mestdagh P, Denecker G, Vandesompele J, Dyer MA, Marine JC (2010) Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo. Cell Death Differ 17(4):633–641. doi:10.1038/cdd.2009.202

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Lesnick JE, Chayt KJ, Bruce DA, Rorke LB, Trojanowski J, Savino PJ, Schatz NJ (1985) Familial pineoblastoma. Report of two cases. J Neurosurg 62(6):930–932. doi:10.3171/jns.1985.62.6.0930

    Article  PubMed  CAS  Google Scholar 

  24. Mamalis N, Font RL, Anderson CW, Monson MC, Williams AT (1992) Concurrent benign teratoid medulloepithelioma and pineoblastoma. Ophthalmic Surg 23(6):403–408

    PubMed  CAS  Google Scholar 

  25. Marees T, Moll AC, Imhof SM, de Boer MR, Ringens PJ, van Leeuwen FE (2010) Re: more about second cancers after retinoblastoma. J Natl Cancer Inst 102(11):831–832. doi:10.1093/jnci/djp207

    Article  PubMed  Google Scholar 

  26. Mena H, Rushing EJ, Ribas JL, Delahunt B, McCarthy WF (1995) Tumors of pineal parenchymal cells: a correlation of histological features, including nucleolar organizer regions, with survival in 35 cases. Hum Pathol 26(1):20–30

    Article  PubMed  CAS  Google Scholar 

  27. Moll AC, Imhof SM, Bouter LM, Kuik DJ, Den Otter W, Bezemer PD, Koten JW, Tan KE (1996) Second primary tumors in patients with hereditary retinoblastoma: a register-based follow-up study, 1945–1994. Int J Cancer 67(4):515–519. doi:10.1002/(SICI)1097-0215(19960807)67:4<515:AID-IJC9>3.0.CO;2-V

    Article  PubMed  CAS  Google Scholar 

  28. Nowakowski TJ, Mysiak KS, O’Leary T, Fotaki V, Pratt T, Price DJ (2013) Loss of functional Dicer in mouse radial glia cell-autonomously prolongs cortical neurogenesis. Dev Biol 382(2):530–537. doi:10.1016/j.ydbio.2013.08.023

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Olsson R (1961) Subcommissural ependyma and pineal organ development in human fetuses. Gen Comp Endocrinol 1:117–123

    Article  PubMed  CAS  Google Scholar 

  30. Peyster RG, Ginsberg F, Hoover ED (1986) Computed tomography of familial pineoblastoma. J Comput Assist Tomogr 10(1):32–33

    Article  PubMed  CAS  Google Scholar 

  31. Priest JR, Williams GM, Manera R, Jenkinson H, Brundler MA, Davis S, Murray TG, Galliani CA, Dehner LP (2011) Ciliary body medulloepithelioma: four cases associated with pleuropulmonary blastoma–a report from the International Pleuropulmonary Blastoma Registry. Br J Ophthalmol 95(7):1001–1005. doi:10.1136/bjo.2010.189779

    Article  PubMed  Google Scholar 

  32. Priest JR, Williams GM, Mize WA, Dehner LP, McDermott MB (2010) Nasal chondromesenchymal hamartoma in children with pleuropulmonary blastoma–a report from the International Pleuropulmonary Blastoma Registry registry. Int J Pediatr Otorhinolaryngol 74(11):1240–1244. doi:10.1016/j.ijporl.2010.07.022

    Article  PubMed  Google Scholar 

  33. Pugh TJ, Yu W, Yang J, Field AL, Ambrogio L, Carter SL, Cibulskis K, Giannikopoulos P, Kiezun A, Kim J, McKenna A, Nickerson E, Getz G, Hoffher S, Messinger YH, Dehner LP, Roberts CW, Rodriguez-Galindo C, Williams GM, Rossi CT, Meyerson M, Hill DA (2014) Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences. Oncogene. doi:10.1038/onc.2014.150

    PubMed  Google Scholar 

  34. Ramasubramanian A, Correa ZM, Augsburger JJ, Sisk RA, Plager DA (2013) Medulloepithelioma in DICER1 syndrome treated with resection. Eye (Lond) 27(7):896–897. doi:10.1038/eye.2013.87

    Article  CAS  Google Scholar 

  35. Ramasubramanian A, Kytasty C, Meadows AT, Shields JA, Leahey A, Shields CL (2013) Incidence of pineal gland cyst and pineoblastoma in children with retinoblastoma during the chemoreduction era. Am J Ophthalmol 156(4):825–829. doi:10.1016/j.ajo.2013.05.023

    Article  PubMed  Google Scholar 

  36. Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O’Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M (2011) DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA 305(1):68–77. doi:10.1001/jama.2010.1910

    Article  PubMed  CAS  Google Scholar 

  37. Rushlow DE, Mol BM, Kennett JY, Yee S, Pajovic S, Thériault BL, Prigoda-Lee NL, Spencer C, Dimaras H, Corson TW, Pang R, Massey C, Godbout R, Jiang Z, Zacksenhaus E, Paton K, Moll AC, Houdayer C, Raizis A, Halliday W, Lam WL, Boutros PC, Lohmann D, Dorsman JC, Gallie BL (2013) Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies. Lancet Oncol 14(4):327–334. doi:10.1016/S1470-2045(13)70045-7

    Article  PubMed  CAS  Google Scholar 

  38. Sabbaghian N, Hamel N, Srivastava A, Albrecht S, Priest JR, Foulkes WD (2012) Germline DICER1 mutation and associated loss of heterozygosity in a pineoblastoma. J Med Genet 49(7):417–419. doi:10.1136/jmedgenet-2012-100898

    Article  PubMed  CAS  Google Scholar 

  39. Sabbaghian N, Srivastava A, Hamel N, Plourde F, Gajtko-Metera M, Niedziela M, Foulkes WD (2013) Germ-line deletion in DICER1 revealed by a novel MLPA assay using synthetic oligonucleotides. Eur J Hum Genet. doi:10.1038/ejhg.2013.215

    PubMed  Google Scholar 

  40. Schild SE, Scheithauer BW, Schomberg PJ, Hook CC, Kelly PJ, Frick L, Robinow JS, Buskirk SJ (1993) Pineal parenchymal tumors. Clinical, pathologic, and therapeutic aspects. Cancer 72(3):870–880

    Article  PubMed  CAS  Google Scholar 

  41. Schultz KA, Harris A, Williams GM, Baldinger S, Doros L, Valusek P, Frazier AL, Dehner LP, Messinger Y, Hill DA (2014) Judicious DICER1 testing and surveillance imaging facilitates early diagnosis and cure of pleuropulmonary blastoma. Pediatr Blood Cancer. doi:10.1002/pbc.25092

    Google Scholar 

  42. Seki M, Yoshida K, Shiraishi Y, Shimamura T, Sato Y, Nishimura R, Okuno Y, Chiba K, Tanaka H, Kato K, Kato M, Hanada R, Nomura Y, Park MJ, Ishida T, Oka A, Igarashi T, Miyano S, Hayashi Y, Ogawa S, Takita J (2014) Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma. Cancer Res. doi:10.1158/0008-5472.CAN-13-2470

    PubMed  Google Scholar 

  43. Shields CL, Meadows AT, Shields JA, Carvalho C, Smith AF (2001) Chemoreduction for retinoblastoma may prevent intracranial neuroblastic malignancy (trilateral retinoblastoma). Arch Ophthalmol 119(9):1269–1272

    Article  PubMed  CAS  Google Scholar 

  44. Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S, Barfoot R, Burke A, Chisholm J, Hewitt M, Jenkinson H, King D, Morland B, Pizer B, Prescott K, Saggar A, Side L, Traunecker H, Vaidya S, Ward P, Futreal PA, Vujanic G, Nicholson AG, Sebire N, Turnbull C, Priest JR, Pritchard-Jones K, Houlston R, Stiller C, Stratton MR, Douglas J, Rahman N (2011) DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48(4):273–278. doi:10.1136/jmg.2010.083790

    Article  PubMed  CAS  Google Scholar 

  45. Tischkowitz M, Xia B, Sabbaghian N, Reis-Filho JS, Hamel N, Li G, van Beers EH, Li L, Khalil T, Quenneville LA, Omeroglu A, Poll A, Lepage P, Wong N, Nederlof PM, Ashworth A, Tonin PN, Narod SA, Livingston DM, Foulkes WD (2007) Analysis of PALB2/FANCN-associated breast cancer families. Proc Natl Acad Sci 104(16):6788–6793. doi:10.1073/pnas.0701724104

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  46. Tomiak E, de Kock L, Grynspan D, Ramphal R, Foulkes WD (2014) DICER1 mutations in an adolescent with cervical embryonal rhabdomyosarcoma (cERMS). Pediatr Blood Cancer 61(3):568–569. doi:10.1002/pbc.24826

    Article  PubMed  Google Scholar 

  47. Turaka K, Shields CL, Meadows AT, Leahey A (2012) Second malignant neoplasms following chemoreduction with carboplatin, etoposide, and vincristine in 245 patients with intraocular retinoblastoma. Pediatr Blood Cancer 59(1):121–125. doi:10.1002/pbc.23278

    Article  PubMed  Google Scholar 

  48. Witkowski L, Mattina J, Schonberger S, Murray MJ, Choong CS, Huntsman DG, Reis-Filho JS, McCluggage WG, Nicholson JC, Coleman N, Calaminus G, Schneider DT, Arseneau J, Stewart CJ, Foulkes WD (2013) DICER1 hotspot mutations in non-epithelial gonadal tumours. Br J Cancer 109(10):2744–2750. doi:10.1038/bjc.2013.637

    Article  PubMed  CAS  Google Scholar 

  49. Wu MK, Sabbaghian N, Xu B, Addidou-Kalucki S, Bernard C, Zou D, Reeve AE, Eccles MR, Cole C, Choong CS, Charles A, Tan TY, Iglesias DM, Goodyer PR, Foulkes WD (2013) Biallelic DICER1 mutations occur in Wilms tumours. J Pathol 230(2):154–164. doi:10.1002/path.4196

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank the Children’s Cancer and Leukaemia Group Tumour Bank for samples, Lisa Storer, Laura Zahavich, Dr Ute Bartels, Dr John-Paul Kilday, Dr Paul Nathan, Dr Armando Lorenzo, Dr Nalin Gupta and Dr Sharon Plon for their assistance with ascertainment and analysis of their respective cases and members of the Baylor-Hopkins Center for Mendelian Genomics their help with the exome sequencing of case 21. We also thank Pierre Lepage and the MUGQIC staff for designing primers for, optimizing and performing the Fluidigm Access Array capture and sequencing, and N. Benlimame (George and Olga Minarik Research Pathology Facility, Jewish General Hospital) for help with immunohistochemical analysis. This research was made possible thanks to the support of Alex’s Lemonade Stand Foundation and The Brain Tumour Charity who fund the CNS PNET research at CBTRC. The identification of a DICER1 mutation in one patient was made by whole exome sequencing conducted at the Center for Mendelian Genomics, funded by The National Institutes of Health (NIH) and supported by the National Human Genome Research Institute grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics.

Conflict of interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Human Genetics, McGill University, Montreal, QC, Canada

    Leanne de Kock & William D. Foulkes

  2. Department of Medical Genetics, The Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, 3755 Cote St. Catherine Road, Montreal, QC, H3T 1E2, Canada

    Leanne de Kock, Nelly Sabbaghian & William D. Foulkes

  3. Division of Haematology/Oncology, The Hospital for Sick Children, The University of Toronto, Toronto, ON, Canada

    Harriet Druker

  4. Department of Molecular and Medical Genetics, The University of Toronto, Toronto, ON, Canada

    Harriet Druker

  5. Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montreal, QC, Canada

    Evan Weber, Nancy Hamel & William D. Foulkes

  6. Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, QC, Canada

    Nancy Hamel & William D. Foulkes

  7. Children’s Brain Tumour Research Center, School of Clinical Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham, UK

    Suzanne Miller & Richard G. Grundy

  8. Child and Adolescent Health Service, Subiaco, WA, Australia

    Catherine S. Choong

  9. Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, WA, Australia

    Catherine S. Choong

  10. Department of Paediatric Oncology/Haematology, Princess Margaret Hospital for Children, Perth, Australia

    Nicholas G. Gottardo

  11. Division of Children’s Leukaemia and Cancer Research, Telethon Kids Institute, The University of Western Australia, Perth, Australia

    Nicholas G. Gottardo

  12. Division of Children’s Leukaemia and Cancer Research, Telethon Kids Institute, The University of Western Australia, Perth, Australia

    Ursula R. Kees

  13. Department of Pediatrics, Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA

    Surya P. Rednam

  14. Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands

    Liselotte P. van Hest

  15. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands

    Marjolijn C. Jongmans

  16. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA

    Shalini Jhangiani & James R. Lupski

  17. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    James R. Lupski

  18. Texas Children’s Hospital, Houston, TX, USA

    James R. Lupski

  19. Department of Endocrinology and Diabetes, Royal Children’s Hospital, Parkville, Melbourne, VIC, Australia

    Margaret Zacharin

  20. Department of Pathology, CHU-Sainte Justine and University of Montreal, Montreal, QC, Canada

    Dorothée Bouron-Dal Soglio

  21. Division of Hematology, The Hospital for Sick Children, Toronto, ON, Canada

    Annie Huang

  22. Minneapolis, MN, USA

    John R. Priest

  23. Departments of Pathology and Neurological Surgery, UCSF Medical Center, San Francisco, CA, USA

    Arie Perry

  24. Departments of Neurology, Pediatrics and Neurosurgery, UCSF Medical Center, San Francisco, CA, USA

    Sabine Mueller

  25. Department of Pathology, Montreal Children’s Hospital and McGill University, Montreal, QC, Canada

    Steffen Albrecht

  26. Division of Haematology/Oncology, The Hospital for Sick Children, The University of Toronto, Toronto, ON, Canada

    David Malkin

  27. Departments of Pediatrics and Medical Biophysics, The University of Toronto, Toronto, ON, Canada

    David Malkin

  28. Department of Paediatrics, University of Toronto, Toronto, ON, Canada

    David Malkin

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  1. Leanne de Kock
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  2. Nelly Sabbaghian
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  3. Harriet Druker
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  4. Evan Weber
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  5. Nancy Hamel
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  6. Suzanne Miller
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  7. Catherine S. Choong
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  8. Nicholas G. Gottardo
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  9. Ursula R. Kees
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  10. Surya P. Rednam
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  11. Liselotte P. van Hest
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  12. Marjolijn C. Jongmans
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  13. Shalini Jhangiani
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  14. James R. Lupski
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  15. Margaret Zacharin
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  16. Dorothée Bouron-Dal Soglio
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  17. Annie Huang
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  18. John R. Priest
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  19. Arie Perry
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  20. Sabine Mueller
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  21. Steffen Albrecht
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  22. David Malkin
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  23. Richard G. Grundy
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  24. William D. Foulkes
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Corresponding author

Correspondence to William D. Foulkes.

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de Kock, L., Sabbaghian, N., Druker, H. et al. Germ-line and somatic DICER1 mutations in pineoblastoma. Acta Neuropathol 128, 583–595 (2014). https://doi.org/10.1007/s00401-014-1318-7

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  • DOI: https://doi.org/10.1007/s00401-014-1318-7

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