1. Academic Validation
  2. Imaging and multi-omics datasets converge to define different neural progenitor origins for ATRT-SHH subgroups

Imaging and multi-omics datasets converge to define different neural progenitor origins for ATRT-SHH subgroups

  • Nat Commun. 2023 Oct 20;14(1):6669. doi: 10.1038/s41467-023-42371-7.
María-Jesús Lobón-Iglesias # 1 Mamy Andrianteranagna # 1 2 Zhi-Yan Han # 1 Céline Chauvin 1 Julien Masliah-Planchon 3 Valeria Manriquez 4 Arnault Tauziede-Espariat 5 6 Sandrina Turczynski 1 Rachida Bouarich-Bourimi 1 Magali Frah 1 Christelle Dufour 7 Thomas Blauwblomme 8 Liesbeth Cardoen 9 Gaelle Pierron 3 Laetitia Maillot 3 Delphine Guillemot 3 Stéphanie Reynaud 3 Christine Bourneix 3 Célio Pouponnot 10 Didier Surdez 11 12 Mylene Bohec 13 Sylvain Baulande 13 Olivier Delattre 3 11 Eliane Piaggio 4 Olivier Ayrault 10 Joshua J Waterfall 14 15 Nicolas Servant 2 Kevin Beccaria 8 Volodia Dangouloff-Ros 16 Franck Bourdeaut 17 18
Affiliations

Affiliations

  • 1 INSERM U830, Laboratory of Translational Research In Pediatric Oncology, PSL Research University, SIREDO Oncology center, Institut Curie Research Center, Paris, France.
  • 2 INSERM U900, Bioinformatics, Biostatistics, Epidemiology and Computational Systems Unit, Institut Curie, Mines Paris Tech, PSL Research University, Institut Curie Research Center, Paris, France.
  • 3 Somatic Genetic Unit, Department of Pathology and Diagnostic and Theranostic Medecine, Institut Curie Hospital, Paris, France.
  • 4 INSERM U932, Immunity and Cancer, PSL Research University, Institut Curie Research Center, Paris, France.
  • 5 Department of Neuropathology, GHU Paris-Psychiatry and Neurosciences, Sainte-Anne Hospital, Paris, France.
  • 6 Paris Psychiatry and Neurosciences Institute (IPNP), UMR S1266, INSERM, IMA-BRAIN, Paris, France.
  • 7 Department of Children and Adolescents Oncology, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • 8 Department of Pediatric Neurosurgery-AP-HP, Necker Sick Kids Hospital, Université de Paris, Paris, France.
  • 9 Imaging Department, Institut Curie Hospital, Paris, France.
  • 10 CNRS UMR 3347, INSERM U1021, Institut Curie, PSL Research University, Université Paris-Saclay, Orsay, France.
  • 11 INSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research Center, Paris, France.
  • 12 Balgrist University Hospital, Faculty of Medicine, University of Zurich (UZH), Zurich, Switzerland.
  • 13 Institut Curie, PSL University, Single Cell Initiative, ICGex Next-Generation Sequencing Platform, PSL University, 75005, Paris, France.
  • 14 INSERM U830, Integrative Functional Genomics of Cancer Lab, PSL Research University, Institut Curie Research Center, Paris, France.
  • 15 Department of Translational Research, PSL Research University, Institut Curie Research Center, Paris, France.
  • 16 Pediatric Radiology Department, AP-HP, Necker Sick Kids Hospital and Paris Cite Universiy INSERM 1299 and UMR 1163, Institut Imagine, Paris, France.
  • 17 INSERM U830, Laboratory of Translational Research In Pediatric Oncology, PSL Research University, SIREDO Oncology center, Institut Curie Research Center, Paris, France. franck.bourdeaut@curie.fr.
  • 18 Department of Pediatric Oncology, SIREDO Oncology Center, Institut Curie Hospital, Paris, and Université de Paris, Paris, France. franck.bourdeaut@curie.fr.
  • # Contributed equally.
Abstract

Atypical teratoid rhabdoid tumors (ATRT) are divided into MYC, TYR and SHH subgroups, suggesting diverse lineages of origin. Here, we investigate the imaging of human ATRT at diagnosis and the precise anatomic origin of brain tumors in the Rosa26-CreERT2::Smarcb1flox/flox model. This cross-species analysis points to an extra-cerebral origin for MYC tumors. Additionally, we clearly distinguish SHH ATRT emerging from the cerebellar anterior lobe (CAL) from those emerging from the basal ganglia (BG) and intra-ventricular (IV) regions. Molecular characteristics point to the midbrain-hindbrain boundary as the origin of CAL SHH ATRT, and to the ganglionic eminence as the origin of BG/IV SHH ATRT. Single-cell RNA Sequencing on SHH ATRT supports these hypotheses. Trajectory analyses suggest that SMARCB1 loss induces a de-differentiation process mediated by repressors of the neuronal program such as REST, ID and the Notch pathway.

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