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

María-Jesús Lobón-Iglesias; Mamy Andrianteranagna; Zhi-Yan Han; Céline Chauvin; Julien Masliah-Planchon; Valeria Manriquez; Arnault Tauziede-Espariat; Sandrina Turczynski; Rachida Bouarich-Bourimi; Magali Frah; Christelle Dufour; Thomas Blauwblomme; Liesbeth Cardoen; Gaelle Pierron; Laetitia Maillot; Delphine Guillemot; Stéphanie Reynaud; Christine Bourneix; Célio Pouponnot; Didier Surdez; Mylene Bohec; Sylvain Baulande; Olivier Delattre; Eliane Piaggio; Olivier Ayrault; Joshua J Waterfall; Nicolas Servant; Kevin Beccaria; Volodia Dangouloff-Ros; Franck Bourdeaut

doi:10.1038/s41467-023-42371-7

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.

Authors

María-Jesús Lobón-Iglesias^#¹, Mamy Andrianteranagna^#^{1

2}, Zhi-Yan Han^#¹, Céline Chauvin¹, Julien Masliah-Planchon³, Valeria Manriquez⁴, Arnault Tauziede-Espariat^{5

6}, Sandrina Turczynski¹, Rachida Bouarich-Bourimi¹, Magali Frah¹, Christelle Dufour⁷, Thomas Blauwblomme⁸, Liesbeth Cardoen⁹, Gaelle Pierron³, Laetitia Maillot³, Delphine Guillemot³, Stéphanie Reynaud³, Christine Bourneix³, Célio Pouponnot¹⁰, Didier Surdez^{11

12}, Mylene Bohec¹³, Sylvain Baulande¹³, Olivier Delattre^{3

11}, Eliane Piaggio⁴, Olivier Ayrault¹⁰, Joshua J Waterfall^{14

15}, Nicolas Servant², Kevin Beccaria⁸, Volodia Dangouloff-Ros¹⁶, Franck Bourdeaut^{17

18}

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-Cre^ERT2::Smarcb1^flox/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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / genetics
Diagnostic Imaging
Hedgehog Proteins / genetics
Humans
Multiomics
Rhabdoid Tumor* / genetics
SMARCB1 Protein / genetics
Teratoma* / pathology
Transcription Factors / genetics

Substances

SMARCB1 Protein
Transcription Factors
SHH protein, human
Hedgehog Proteins