Skip to main content
SpringerLink
Log in

Molecular subgrouping of primary pineal parenchymal tumors reveals distinct subtypes correlated with clinical parameters and genetic alterations

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Tumors of the pineal region comprise several different entities with distinct clinical and histopathological features. Whereas some entities predominantly affect adults, pineoblastoma (PB) constitutes a highly aggressive malignancy of childhood with a poor outcome. PBs mainly arise sporadically, but may also occur in the context of cancer predisposition syndromes including DICER1 and RB1 germline mutation. With this study, we investigate clinico-pathological subgroups of pineal tumors and further characterize their biological features. We performed genome-wide DNA methylation analysis in 195 tumors of the pineal region and 20 normal pineal gland controls. Copy-number profiles were obtained from DNA methylation data; gene panel sequencing was added for 93 tumors and analysis was further complemented by miRNA sequencing for 22 tumor samples. Unsupervised clustering based on DNA methylation profiling separated known subgroups, like pineocytoma, pineal parenchymal tumor of intermediate differentiation, papillary tumor of the pineal region and PB, and further distinct subtypes within these groups, including three subtypes within the core PB subgroup. The novel molecular subgroup Pin-RB includes cases of trilateral retinoblastoma as well as sporadic pineal tumors with RB1 alterations, and displays similarities with retinoblastoma. Distinct clinical associations discriminate the second novel molecular subgroup PB-MYC from other PB cases. Alterations within the miRNA processing pathway (affecting DROSHA, DGCR8 or DICER1) are found in about two thirds of cases in the three core PB subtypes. Methylation profiling revealed biologically distinct groups of pineal tumors with specific clinical and molecular features. Our findings provide a foundation for further clinical as well as molecular and functional characterization of PB and other pineal tumors, including the role of miRNA processing defects in oncogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Anglesio MS, Wang Y, Yang W, Senz J, Wan A, Heravi-Moussavi A et al (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 229:400–409. https://doi.org/10.1002/path.4135

    Article  CAS  PubMed  Google Scholar 

  2. Blanquet V, Turleau C, Gross-Morand MS, Senamaud-Beaufort C, Doz F, Besmond C (1995) Spectrum of germline mutations in the RB1 gene: a study of 232 patients with hereditary and non hereditary retinoblastoma. Hum Mol Genet 4:383–388. https://doi.org/10.1093/hmg/4.3.383

    Article  CAS  PubMed  Google Scholar 

  3. Bohrnsen F, Enders C, Ludwig HC, Bruck W, Fuzesi L, Gutenberg A (2015) Common molecularcytogenetic alterations in tumors originating from the pineal region. Oncol Lett 10(3):1853–1857. https://doi.org/10.3892/ol.2015.3383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D et al (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469–474. https://doi.org/10.1038/nature26000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Consortium EP (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74. https://doi.org/10.1038/nature11247

    Article  CAS  Google Scholar 

  6. de Jong MC, Kors WA, de Graaf P, Castelijns JA, Kivela T, Moll AC (2014) Trilateral retinoblastoma: a systematic review and meta-analysis. Lancet Oncol 15:1157–1167. https://doi.org/10.1016/S1470-2045(14)70336-5

    Article  PubMed  Google Scholar 

  7. de Jong MC, Kors WA, de Graaf P, Castelijns JA, Moll AC, Kivela T (2015) The incidence of trilateral retinoblastoma: a systematic review and meta-analysis. Am J Ophthalmol 160(1116–1126):e5. https://doi.org/10.1016/j.ajo.2015.09.009

    Article  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dimaras H, Kimani K, Dimba EA, Gronsdahl P, White A, Chan HS et al (2012) Retinoblastoma. Lancet 379:1436–1446. https://doi.org/10.1016/S0140-6736(11)61137-9

    Article  PubMed  Google Scholar 

  10. Farnia B, Allen PK, Brown PD, Khatua S, Levine NB, Li J et al (2014) Clinical outcomes and patterns of failure in pineoblastoma: a 30-year, single-institution retrospective review. World neurosurg 82:1232–1241. https://doi.org/10.1016/j.wneu.2014.07.010

    Article  PubMed  Google Scholar 

  11. Foulkes WD, Priest JR, Duchaine TF (2014) DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer 14:662–672. https://doi.org/10.1038/nrc3802

    Article  CAS  PubMed  Google Scholar 

  12. Frankish A, Diekhans M, Ferreira AM, Johnson R, Jungreis I, Loveland J et al (2019) GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res 47:D766–D773. https://doi.org/10.1093/nar/gky955

    Article  CAS  PubMed  Google Scholar 

  13. Friedrich C, von Bueren AO, von Hoff K, Gerber NU, Ottensmeier H, Deinlein F et al (2013) Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy. Neuro Oncol 15:224–234. https://doi.org/10.1093/neuonc/nos292

    Article  CAS  PubMed  Google Scholar 

  14. Gadd S, Huff V, Walz AL, Ooms A, Armstrong AE, Gerhard DS et al (2017) A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nat Genet 49:1487–1494. https://doi.org/10.1038/ng.3940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gerber NU, von Hoff K, Resch A, Ottensmeier H, Kwiecien R, Faldum A et al (2014) Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy. Int J Radiat Oncol Biol Phys 89:863–871. https://doi.org/10.1016/j.ijrobp.2014.04.017

    Article  PubMed  Google Scholar 

  16. Goschzik T, Gessi M, Denkhaus D, Pietsch T (2014) PTEN mutations and activation of the PI3K/Akt/mTOR signaling pathway in papillary tumors of the pineal region. J Neuropathol Exp Neurol 73:747–751. https://doi.org/10.1097/NEN.0000000000000093

    Article  CAS  PubMed  Google Scholar 

  17. Gratias S, Schuler A, Hitpass LK, Stephan H, Rieder H, Schneider S et al (2005) Genomic gains on chromosome 1q in retinoblastoma: consequences on gene expression and association with clinical manifestation. Int J Cancer 116:555–563. https://doi.org/10.1002/ijc.21051

    Article  CAS  PubMed  Google Scholar 

  18. Gustmann S, Klein-Hitpass L, Stephan H, Weber S, Bornfeld N, Kaulisch M et al (2011) Loss at chromosome arm 16q in retinoblastoma: confirmation of the association with diffuse vitreous seeding and refinement of the recurrently deleted region. Genes Chromosomes Cancer 50:327–337. https://doi.org/10.1002/gcc.20857

    Article  CAS  PubMed  Google Scholar 

  19. Heim S, Sill M, Jones DT, Vasiljevic A, Jouvet A, Fevre-Montange M et al (2016) Papillary tumor of the pineal region: a distinct molecular entity. Brain Pathol 26:199–205. https://doi.org/10.1111/bpa.12282

    Article  CAS  PubMed  Google Scholar 

  20. Heravi-Moussavi A, Anglesio MS, Cheng SW, Senz J, Yang W, Prentice L et al (2012) Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med 366:234–242. https://doi.org/10.1056/NEJMoa1102903

    Article  CAS  PubMed  Google Scholar 

  21. Hwang EI, Kool M, Burger PC, Capper D, Chavez L, Brabetz S et al (2018) Extensive molecular and clinical heterogeneity in patients with histologically diagnosed CNS-PNET treated as a single entity: a report from the Children's Oncology Group Randomized ACNS0332 Trial. J Clin Oncol. https://doi.org/10.1200/JCO.2017.76.4720

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kaatsch P, Grabow D, Spix C (2018) German Childhood Cancer Registry—annual report 2018 (1980–2017). https://www.kinderkrebsregister.de/typo3temp/secure_downloads/22605/0/2df4719687ba2596d4216218a4f4632763b64847/jb2018s.pdf. Accessed 7 Nov 2019

  23. Kline CN, Joseph NM, Grenert JP, van Ziffle J, Talevich E, Onodera C (2017) Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy. Neuro Oncol 19(5):699–709. https://doi.org/10.1093/neuonc/now254

    Article  CAS  PubMed  Google Scholar 

  24. Koelsche C, Mynarek M, Schrimpf D, Bertero L, Serrano J, Sahm F et al (2018) Primary intracranial spindle cell sarcoma with rhabdomyosarcoma-like features share a highly distinct methylation profile and DICER1 mutations. Acta Neuropathol 136:327–337. https://doi.org/10.1007/s00401-018-1871-6

    Article  CAS  PubMed  Google Scholar 

  25. Kozomara A, Griffiths-Jones S (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39:D152–157. https://doi.org/10.1093/nar/gkq1027

    Article  CAS  PubMed  Google Scholar 

  26. Lee JC, Mazor T, Lao R, Wan E, Diallo AB, Hill NS et al (2019) Recurrent KBTBD4 small in-frame insertions and absence of DROSHA deletion or DICER1 mutation differentiate pineal parenchymal tumor of intermediate differentiation (PPTID) from pineoblastoma. Acta Neuropathol. https://doi.org/10.1007/s00401-019-01990-5

    Article  PubMed  PubMed Central  Google Scholar 

  27. Li MH, Bouffet E, Hawkins CE, Squire JA, Huang A (2005) Molecular genetics of supratentorial primitive neuroectodermal tumors and pineoblastoma. Neurosurg Focus 19:E3

    PubMed  Google Scholar 

  28. Lillington DM, Kingston JE, Coen PG, Price E, Hungerford J, Domizio P et al (2003) Comparative genomic hybridization of 49 primary retinoblastoma tumors identifies chromosomal regions associated with histopathology, progression, and patient outcome. Genes Chromosomes Cancer 36:121–128. https://doi.org/10.1002/gcc.10149

    Article  CAS  PubMed  Google Scholar 

  29. Lohmann DR (1999) RB1 gene mutations in retinoblastoma. Hum Mutat 14:283–288. https://doi.org/10.1002/(SICI)1098-1004(199910)14:4%3c283:AID-HUMU2%3e3.0.CO;2-J

    Article  CAS  PubMed  Google Scholar 

  30. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) (2016) WHO classification of tumour of the central nervous system, 4th edn. IARC, Lyon

    Google Scholar 

  31. Miller S, Rogers HA, Lyon P, Rand V, Adamowicz-Brice M, Clifford SC et al (2011) Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma. Neuro Oncol 13:866–879. https://doi.org/10.1093/neuonc/nor070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mynarek M, Pizer B, Dufour C, van Vuurden D, Garami M, Massimino M et al (2017) Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma: analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data. Neuro Oncol 19:576–585. https://doi.org/10.1093/neuonc/now234

    Article  CAS  PubMed  Google Scholar 

  33. Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J, Ehrenberger T et al (2017) The whole-genome landscape of medulloblastoma subtypes. Nature 547:311–317. https://doi.org/10.1038/nature22973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T et al (2012) Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature 488:49–56. https://doi.org/10.1038/nature11327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS (2018) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro Oncol 20:iv1–iv86. https://doi.org/10.1093/neuonc/noy131

    Article  PubMed  PubMed Central  Google Scholar 

  36. Parikh KA, Venable GT, Orr BA, Choudhri AF, Boop FA, Gajjar AJ et al (2017) Pineoblastoma—the experience at St Jude Children's Research Hospital. Neurosurgery 81:120–128. https://doi.org/10.1093/neuros/nyx005

    Article  PubMed  Google Scholar 

  37. Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222. https://doi.org/10.1038/nrd.2016.246

    Article  CAS  PubMed  Google Scholar 

  38. Sahm F, Schrimpf D, Jones DT, Meyer J, Kratz A, Reuss D et al (2016) Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets. Acta Neuropathol 131:903–910. https://doi.org/10.1007/s00401-015-1519-8

    Article  CAS  PubMed  Google Scholar 

  39. Schild SE, Scheithauer BW, Schomberg PJ, Hook CC, Kelly PJ, Frick L et al (1993) Pineal parenchymal tumors. Clinical, pathologic, and therapeutic aspects. Cancer 72:870–880

    Article  CAS  PubMed  Google Scholar 

  40. Schultz KA, Yang J, Doros L, Williams GM, Harris A, Stewart DR et al (2014) DICER1-pleuropulmonary blastoma familial tumor predisposition syndrome: a unique constellation of neoplastic conditions. Pathol Case Rev 19:90–100. https://doi.org/10.1097/PCR.0000000000000027

    Article  PubMed  PubMed Central  Google Scholar 

  41. Schultz KAP, Rednam SP, Kamihara J, Doros L, Achatz MI, Wasserman JD et al (2017) PTEN, DICER1, FH, and their associated tumor susceptibility syndromes: clinical features, genetics, and surveillance recommendations in childhood. Clin Cancer Res 23(12):e76–e82. https://doi.org/10.1158/1078-0432.CCR-17-0629

    Article  CAS  PubMed  Google Scholar 

  42. Shukla GC, Singh J, Barik S (2011) MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol 3:83–92

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Snuderl M, Kannan K, Pfaff E, Wang S, Stafford JM, Serrano J et al (2018) Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma. Nat Commun 9:2868. https://doi.org/10.1038/s41467-018-05029-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D et al (2016) New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell 164:1060–1072. https://doi.org/10.1016/j.cell.2016.01.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. von Bueren AO, Gerss J, Hagel C, Cai H, Remke M, Hasselblatt M (2012) DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis. J Neurooncol 109(2):415–423. https://doi.org/10.1007/s11060-012-0911-7

    Article  CAS  Google Scholar 

  46. Wegert J, Ishaque N, Vardapour R, Georg C, Gu Z, Bieg M et al (2015) Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors. Cancer Cell 27:298–311. https://doi.org/10.1016/j.ccell.2015.01.002

    Article  CAS  PubMed  Google Scholar 

  47. Worst BC, van Tilburg CM, Balasubramanian GP, Fiesel P, Witt R, Freitag A et al (2016) Next-generation personalised medicine for high-risk paediatric cancer patients—the INFORM pilot study. Eur J Cancer 65:91–101. https://doi.org/10.1016/j.ejca.2016.06.009

    Article  PubMed  Google Scholar 

  48. Yamanaka R, Hayano A, Takashima Y (2017) Trilateral retinoblastoma: a systematic review of 211 cases. Neurosurg Rev 42:39–48. https://doi.org/10.1007/s10143-017-0890-4

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center (to Matthias A. Karajannis). Christian Thomas has been supported by Innovative Medizinische Forschung Münster (IMF TH 111807). Grants from the Friedberg Charitable Foundation, the Sohn Conference Foundation and the Making Headway Foundation were provided to Matija Snuderl.

Author information

Authors and Affiliations

  1. Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany

    Elke Pfaff, Martin Sill, Andrea Wittmann, Anna Kaufhold, Felix Sahm, Marcel Kool, Stefan M. Pfister & David T. W. Jones

  2. Pediatric Glioma Research Group (B360), German Cancer Research Center (DKFZ), Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany

    Elke Pfaff, Andrea Wittmann & David T. W. Jones

  3. Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany

    Elke Pfaff & Stefan M. Pfister

  4. Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Christian Aichmüller, Murat Iskar, Peter Lichter & Marc Zapatka

  5. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Martin Sill, Anna Kaufhold, Marcel Kool & Stefan M. Pfister

  6. Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany

    Damian Stichel, Andrey Korshunov, Felix Sahm & Andreas von Deimling

  7. Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany

    Damian Stichel, Andrey Korshunov, Felix Sahm & Andreas von Deimling

  8. Division of Neuropathology, NYU Langone Health, New York, USA

    Matija Snuderl

  9. Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, USA

    Matija Snuderl

  10. Division of Molecular Pathology and Diagnostics, NYU Langone Health, New York, USA

    Matija Snuderl

  11. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, USA

    Matthias A. Karajannis

  12. Division of Pediatric Neurosurgery, Department of Neurosurgery, Eberhard Karl’s University Hospital of Tübingen, Tübingen, Germany

    Martin U. Schuhmann

  13. Institute of Neuropathology, Department of Pathology and Neuropathology, University of Tübingen, Comprehensive Cancer Center Tübingen-Stuttgart, Tübingen, Germany

    Jens Schittenhelm

  14. Institute of Neuropathology, University Hospital Münster, Munster, Germany

    Martin Hasselblatt & Christian Thomas

  15. Department of Neuropathology, Burdenko Neurosurgical Institute, Moscow, Russia

    Marina Rhizova

  16. Pediatrics III, Pediatric Oncology and Hematology, University Hospital Essen, Essen, Germany

    Petra Ketteler

  17. Eye Cancer Genetics, Institute of Human Genetics, University Hospital Essen, Essen, Germany

    Dietmar Lohmann

  18. Department of Pathology, St. Jude Children’s Research Hospital, Memphis, USA

    Brent A. Orr & David W. Ellison

  19. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, USA

    David W. Ellison

  20. Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Katja von Hoff

  21. Department of Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany

    Katja von Hoff, Martin Mynarek & Stefan Rutkowski

  22. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

    Peter Lichter

Authors
  1. Elke Pfaff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Aichmüller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Sill
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Damian Stichel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matija Snuderl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matthias A. Karajannis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martin U. Schuhmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jens Schittenhelm
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Martin Hasselblatt
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Christian Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Andrey Korshunov
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Marina Rhizova
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Andrea Wittmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Anna Kaufhold
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Murat Iskar
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Petra Ketteler
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Dietmar Lohmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Brent A. Orr
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. David W. Ellison
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Katja von Hoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Martin Mynarek
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Stefan Rutkowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Felix Sahm
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Andreas von Deimling
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Peter Lichter
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Marcel Kool
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Marc Zapatka
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Stefan M. Pfister
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. David T. W. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David T. W. Jones.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

401_2019_2101_MOESM1_ESM.tif

Supplementary figure 1: Comparing 3’/5’miRNA expression across samples, the expression of 5’ miRNA was on average slightly higher (each column pair represents one case) (a). The PB subtypes displayed a lower fraction of completely processed miRNA in relation to all miRNA (miRNA: #Mature/(#Hairpin + #Mature)) (b). Detailed small RNA composition for the individual subtypes (c). (TIF 97463 kb)

Supplementary table 1: List of genes included in the next-generation sequencing (NGS) gene panel (DOCX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pfaff, E., Aichmüller, C., Sill, M. et al. Molecular subgrouping of primary pineal parenchymal tumors reveals distinct subtypes correlated with clinical parameters and genetic alterations. Acta Neuropathol 139, 243–257 (2020). https://doi.org/10.1007/s00401-019-02101-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-019-02101-0

Keywords

Search

Navigation