Preneoplastic liver colonization by 11p15.5 altered mosaic cells in young children with hepatoblastoma

Jill Pilet, Theo Z. Hirsch, Barkha Gupta, Amélie Roehrig, Guillaume Morcrette, Aurore Pire, Eric Letouzé, Brice Fresneau, Sophie Taque, Laurence Brugières, Sophie Branchereau, Christophe Chardot, Isabelle Aerts, Sabine Sarnacki, Monique Fabre, Catherine Guettier, Sandra Rebouissou and Jessica Zucman-Rossi ()
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Jill Pilet: Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm
Theo Z. Hirsch: Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm
Barkha Gupta: Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm
Amélie Roehrig: Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm
Guillaume Morcrette: Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm
Aurore Pire: Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm
Eric Letouzé: Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm
Brice Fresneau: Gustave Roussy, Université Paris-Saclay, Department of Children and Adolescents Oncology
Sophie Taque: CHU Rennes
Laurence Brugières: Gustave Roussy, Université Paris-Saclay, Department of Children and Adolescents Oncology
Sophie Branchereau: Paris-Saclay University
Christophe Chardot: Université Paris Cité
Isabelle Aerts: Institut Curie, PSL Research University, Oncology Center SIREDO
Sabine Sarnacki: Université Paris Cité
Monique Fabre: Pathology Department, Necker Enfants Malades Hospital, Université Paris Cité, AP-HP
Catherine Guettier: Paris-Saclay University
Sandra Rebouissou: Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm
Jessica Zucman-Rossi: Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Pediatric liver tumors are very rare tumors with the most common diagnosis being hepatoblastoma. While hepatoblastomas are predominantly sporadic, around 15% of cases develop as part of predisposition syndromes such as Beckwith-Wiedemann (11p15.5 locus altered). Here, we identify mosaic genetic alterations of 11p15.5 locus in the liver of hepatoblastoma patients without a clinical diagnosis of Beckwith-Wiedemann syndrome. We do not retrieve these alterations in children with other types of pediatric liver tumors. We show that mosaic 11p15.5 alterations in liver FFPE sections of hepatoblastoma patients display IGF2 overexpression and H19 downregulation together with an alteration of the liver zonation. Moreover, mosaic livers’ microenvironment is enriched in extracellular matrix and angiogenesis. Spatial transcriptomics and single-nucleus RNAseq analyses identify a 60-gene signature in 11p15.5 altered hepatocytes. These data provide insights for 11p15.5 mosaicism detection and its functional consequences during the early steps of carcinogenesis.

Date: 2023
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DOI: 10.1038/s41467-023-42418-9

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