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Two molecularly distinct atypical teratoid/rhabdoid tumors (or tumor components) occurring in an infant with rhabdoid tumor predisposition syndrome 1

  • Christian Thomas
  • Friederike Knerlich-Lukoschus
  • Harald Reinhard
  • Pascal D. Johann
  • Dominik Sturm
  • Felix Sahm
  • Susanne Bens
  • Julia Vogt
  • Karolina Nemes
  • Florian Oyen
  • Uwe Kordes
  • Reiner Siebert
  • Reinhard Schneppenheim
  • Martina Messing-Jünger
  • Torsten Pietsch
  • Andreas von Deimling
  • Werner Paulus
  • Stefan M. Pfister
  • Marcel Kool
  • Michael C. Frühwald
  • Martin HasselblattEmail author
Correspondence

Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly arising in young children [1]. Biallelic mutations of the SWI/SNF chromatin remodeling complex members SMARCB1 or (rarely) SMARCA4 are the only recurrent genetic alterations [1, 2]. The pathogenesis follows a classical two-hit model and heterozygous germline mutations of SMARCB1 (associated with rhabdoid tumor predisposition syndrome 1) or SMARCA4 (rhabdoid tumor predisposition syndrome 2) constitute the first hit in up to 35% of cases [1]. While ATRT is a remarkably homogenous disease on a genetic level, DNA methylation profiles, enhancer landscapes and subgroup-specific transcriptional networks separate ATRT into three distinct molecular subgroups, i.e., ATRT-SHH, ATRT-TYR and ATRT-MYC [3, 4, 5]. These subgroups differ with regard to the age of onset, tumor location and imaging features [3, 4, 5, 6]. As there may also be differences in response to different therapies and overall survival [7],...

Notes

Funding

MH is supported by DFG (HA 3060/8-1).

Supplementary material

401_2019_2001_MOESM1_ESM.pdf (292 kb)
Supplementary material 1 (PDF 292 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Christian Thomas
    • 1
  • Friederike Knerlich-Lukoschus
    • 2
  • Harald Reinhard
    • 2
  • Pascal D. Johann
    • 3
    • 4
    • 5
    • 6
  • Dominik Sturm
    • 3
    • 4
    • 5
    • 6
  • Felix Sahm
    • 3
    • 6
    • 7
    • 8
  • Susanne Bens
    • 9
  • Julia Vogt
    • 9
  • Karolina Nemes
    • 10
  • Florian Oyen
    • 11
  • Uwe Kordes
    • 11
  • Reiner Siebert
    • 9
  • Reinhard Schneppenheim
    • 11
  • Martina Messing-Jünger
    • 2
  • Torsten Pietsch
    • 12
  • Andreas von Deimling
    • 6
    • 7
    • 8
  • Werner Paulus
    • 1
  • Stefan M. Pfister
    • 3
    • 4
    • 5
    • 6
  • Marcel Kool
    • 3
    • 4
    • 6
  • Michael C. Frühwald
    • 10
  • Martin Hasselblatt
    • 1
    Email author
  1. 1.Institute of NeuropathologyUniversity Hospital MünsterMünsterGermany
  2. 2.Asklepios Kinderklinik Sankt AugustinSt. AugustinGermany
  3. 3.Hopp-Children’s Cancer Center (KiTZ)HeidelbergGermany
  4. 4.Division of Pediatric NeurooncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  5. 5.Department of Pediatric Hematology and OncologyUniversity Hospital HeidelbergHeidelbergGermany
  6. 6.German Cancer Consortium (DKTK)HeidelbergGermany
  7. 7.Department of Neuropathology, Institute of PathologyUniversity Hospital HeidelbergHeidelbergGermany
  8. 8.Clinical Cooperation Unit NeuropathologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  9. 9.Institute of Human GeneticsUniversity of Ulm and Ulm University HospitalUlmGermany
  10. 10.University Children’s Hospital AugsburgSwabian Children’s Cancer CenterAugsburgGermany
  11. 11.Department of Pediatric Hematology and OncologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  12. 12.Institute of Neuropathology and DGNN Brain Tumor Reference CentreUniversity of BonnBonnGermany

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