title: The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation.
abstract: Rhabdoid tumours (RTs) are highly aggressive tumours of infancy, frequently localized in the central nervous system (CNS) where they are termed atypical teratoid/rhabdoid tumours (AT/RTs) and characterized by bi-allelic inactivation of the SMARCB1 tumour suppressor gene. In this study, by temporal control of tamoxifen injection in Smarcb1(flox/flox);Rosa26-Cre(ERT2) mice, we explore the phenotypes associated with Smarcb1 inactivation at different developmental stages. Injection before E6, at birth or at 2 months of age recapitulates previously described phenotypes including embryonic lethality, hepatic toxicity or development of T-cell lymphomas, respectively. Injection between E6 and E10 leads to high penetrance tumours, mainly intra-cranial, with short delays (median: 3 months). These tumours demonstrate anatomical, morphological and gene expression profiles consistent with those of human AT/RTs. Moreover, intra- and inter-species comparisons of tumours reveal that human and mouse RTs can be split into different entities that may underline the variety of RT cells of origin.
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, InsermU830, Laboratoire de Genetique et Biologie des Cancers, 26 rue d'Ulm, 75005 Paris, France.|SiRIC- Institut Curie, Laboratoire de Recherche Translationnelle en Oncologie Pédiatrique, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Zhi-Yan
authors.initials: ZY
authors.lastname: Han
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, InsermU830, Laboratoire de Genetique et Biologie des Cancers, 26 rue d'Ulm, 75005 Paris, France.|SiRIC- Institut Curie, Laboratoire de Recherche Translationnelle en Oncologie Pédiatrique, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Wilfrid
authors.initials: W
authors.lastname: Richer
authors.affiliation: Département de Biologie des Tumeurs, Institut Curie, Service d'anatomie pathologique, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Fréneaux
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, InsermU830, Laboratoire de Genetique et Biologie des Cancers, 26 rue d'Ulm, 75005 Paris, France.|SiRIC- Institut Curie, Laboratoire de Recherche Translationnelle en Oncologie Pédiatrique, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Chauvin
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, InsermU830, Laboratoire de Genetique et Biologie des Cancers, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Carlo
authors.initials: C
authors.lastname: Lucchesi
authors.affiliation: Institut Bergonie, Institut Curie, Unité de génétique somatique, Département de Biologie des Tumeurs, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Guillemot
authors.affiliation: Institut Bergonie, Institut Curie, Unité de génétique somatique, Département de Biologie des Tumeurs, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Grison
authors.affiliation: Institut Bergonie, Institut Curie, Unité de génétique somatique, Département de Biologie des Tumeurs, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Lequin
authors.affiliation: Institut Bergonie, Institut Curie, Unité de génétique somatique, Département de Biologie des Tumeurs, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Institut Bergonie, Institut Curie, Unité de génétique somatique, Département de Biologie des Tumeurs, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Masliah-Planchon
authors.affiliation: Institut Curie, Plateforme de pathologie expérimentale, Département de Biologie des Tumeurs, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Nicolas
authors.affiliation: Centre Léon Bérard, Departement de Biopathologie, 28 Promenade Léa et Napoléon Bullukian, 69008 Lyon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Ranchère-Vince
authors.affiliation: Departement de neuropathology, Hopital Sainte-Anne, 1 rue Cabanis, 75014 Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Varlet
authors.affiliation: Université Paris Descartes, 75006 Paris, France.|Service de neurochirurgie pédiatrique, Hopital Necker, 149 rue de Sèvres, 75015 Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Puget
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, InsermU830, Laboratoire de Genetique et Biologie des Cancers, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Janoueix-Lerosey
authors.affiliation: Institut Curie, Paris Sciences et Lettres University Research, CNRS UMR 3306, INSERM U1005, Centre Universitaire d'Orsay, 91898 Orsay, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Ayrault
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, InsermU830, Laboratoire de Genetique et Biologie des Cancers, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Didier
authors.identifier: http://orcid.org/0000-0002-7118-7859
authors.initials: D
authors.lastname: Surdez
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, InsermU830, Laboratoire de Genetique et Biologie des Cancers, 26 rue d'Ulm, 75005 Paris, France.|Institut Bergonie, Institut Curie, Unité de génétique somatique, Département de Biologie des Tumeurs, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, InsermU830, Laboratoire de Genetique et Biologie des Cancers, 26 rue d'Ulm, 75005 Paris, France.|SiRIC- Institut Curie, Laboratoire de Recherche Translationnelle en Oncologie Pédiatrique, 26 rue d'Ulm, 75005 Paris, France.|Département d'oncologie pédiatrique, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051379:Mice; D018335:Rhabdoid Tumor / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000071796:SMARCB1 Protein; D013629:Tamoxifen / Q000633:toxicity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C513265:Smarcb1 protein, mouse; D014157:Transcription Factors; D013629:Tamoxifen
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