Germ-line and somatic DICER1 mutations in pineoblastoma

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• 作者：Leanne de Kock (1) (2)
  Nelly Sabbaghian (2)
  Harriet Druker (3) (4)
  Evan Weber (5)
  Nancy Hamel (5) (6)
  Suzanne Miller (7)
  Catherine S. Choong (8) (9)
  Nicholas G. Gottardo (10) (11)
  Ursula R. Kees (12)
  Surya P. Rednam (13)
  Liselotte P. van Hest (14)
  Marjolijn C. Jongmans (15)
  Shalini Jhangiani (16)
  James R. Lupski (16) (17) (18)
  Margaret Zacharin (19)
  Doroth茅e Bouron-Dal Soglio (20)
  Annie Huang (21)
  John R. Priest (22)
  Arie Perry (23)
  Sabine Mueller (24)
  Steffen Albrecht (25)
  David Malkin (26) (27) (28)
  Richard G. Grundy (7)
  William D. Foulkes (1) (2) (5) (6)
  
• 关键词：DICER1 ; miRNA processing ; Paediatric brain tumours ; Pineal gland ; Childhood cancer ; Mutation ; Pineoblastoma ; OMIM #601200
• 刊名：Acta Neuropathologica
• 出版年：2014
• 出版时间：October 2014
• 年：2014
• 卷：128
• 期：4
• 页码：583-595
• 全文大小：2,854 KB
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  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
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  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 dx.doi.org/10.1126/science.1174334" target="_blank" title="It opens in new window">CrossRef
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• 作者单位：Leanne de Kock (1) (2)
  Nelly Sabbaghian (2)
  Harriet Druker (3) (4)
  Evan Weber (5)
  Nancy Hamel (5) (6)
  Suzanne Miller (7)
  Catherine S. Choong (8) (9)
  Nicholas G. Gottardo (10) (11)
  Ursula R. Kees (12)
  Surya P. Rednam (13)
  Liselotte P. van Hest (14)
  Marjolijn C. Jongmans (15)
  Shalini Jhangiani (16)
  James R. Lupski (16) (17) (18)
  Margaret Zacharin (19)
  Doroth茅e Bouron-Dal Soglio (20)
  Annie Huang (21)
  John R. Priest (22)
  Arie Perry (23)
  Sabine Mueller (24)
  Steffen Albrecht (25)
  David Malkin (26) (27) (28)
  Richard G. Grundy (7)
  William D. Foulkes (1) (2) (5) (6)
  
  1. Department of Human Genetics, McGill University, Montreal, QC, Canada
  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
  3. Division of Haematology/Oncology, The Hospital for Sick Children, The University of Toronto, Toronto, ON, Canada
  4. Department of Molecular and Medical Genetics, The University of Toronto, Toronto, ON, Canada
  5. Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
  6. Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, QC, Canada
  7. Children鈥檚 Brain Tumour Research Center, School of Clinical Sciences, Queen鈥檚 Medical Centre, University of Nottingham, Nottingham, UK
  8. Child and Adolescent Health Service, Subiaco, WA, Australia
  9. Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, WA, Australia
  10. Department of Paediatric Oncology/Haematology, Princess Margaret Hospital for Children, Perth, Australia
  11. Division of Children鈥檚 Leukaemia and Cancer Research, Telethon Kids Institute, The University of Western Australia, Perth, Australia
  12. Division of Children鈥檚 Leukaemia and Cancer Research, Telethon Kids Institute, The University of Western Australia, Perth, Australia
  13. Department of Pediatrics, Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA
  14. Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
  15. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
  16. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA
  17. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  18. Texas Children鈥檚 Hospital, Houston, TX, USA
  19. Department of Endocrinology and Diabetes, Royal Children鈥檚 Hospital, Parkville, Melbourne, VIC, Australia
  20. Department of Pathology, CHU-Sainte Justine and University of Montreal, Montreal, QC, Canada
  21. Division of Hematology, The Hospital for Sick Children, Toronto, ON, Canada
  22. Minneapolis, MN, USA
  23. Departments of Pathology and Neurological Surgery, UCSF Medical Center, San Francisco, CA, USA
  24. Departments of Neurology, Pediatrics and Neurosurgery, UCSF Medical Center, San Francisco, CA, USA
  25. Department of Pathology, Montreal Children鈥檚 Hospital and McGill University, Montreal, QC, Canada
  26. Division of Haematology/Oncology, The Hospital for Sick Children, The University of Toronto, Toronto, ON, Canada
  27. Departments of Pediatrics and Medical Biophysics, The University of Toronto, Toronto, ON, Canada
  28. Department of Paediatrics, University of Toronto, Toronto, ON, Canada
  
• ISSN：1432-0533

文摘

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.