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

Author

Listed:
  • 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
    Department of Oncology, Hopital Européen Georges Pompidou)

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.

Suggested Citation

  • Jill Pilet & Theo Z. Hirsch & Barkha Gupta & Amélie Roehrig & Guillaume Morcrette & Aurore Pire & Eric Letouzé & Brice Fresneau & Sophie Taque & Laurence Brugières & Sophie Branchereau & Christophe Ch, 2023. "Preneoplastic liver colonization by 11p15.5 altered mosaic cells in young children with hepatoblastoma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42418-9
    DOI: 10.1038/s41467-023-42418-9
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    References listed on IDEAS

    as
    1. Jean Charles Nault & Maxime Mallet & Camilla Pilati & Julien Calderaro & Paulette Bioulac-Sage & Christophe Laurent & Alexis Laurent & Daniel Cherqui & Charles Balabaud & Jessica Zucman-Rossi, 2013. "High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions," Nature Communications, Nature, vol. 4(1), pages 1-7, October.
    2. Genta Nagae & Shogo Yamamoto & Masashi Fujita & Takanori Fujita & Aya Nonaka & Takayoshi Umeda & Shiro Fukuda & Kenji Tatsuno & Kazuhiro Maejima & Akimasa Hayashi & Sho Kurihara & Masato Kojima & Tomo, 2021. "Genetic and epigenetic basis of hepatoblastoma diversity," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Amy T. Hark & Christopher J. Schoenherr & David J. Katz & Robert S. Ingram & John M. Levorse & Shirley M. Tilghman, 2000. "CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus," Nature, Nature, vol. 405(6785), pages 486-489, May.
    4. Fabio Iannelli & Agnese Collino & Shruti Sinha & Enrico Radaelli & Paola Nicoli & Lorenzo D’Antiga & Aurelio Sonzogni & Jamila Faivre & Marie Annick Buendia & Ekkehard Sturm & Richard J. Thompson & A., 2014. "Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
    5. Jean Charles Nault & Maxime Mallet & Camilla Pilati & Julien Calderaro & Paulette Bioulac-Sage & Christophe Laurent & Alexis Laurent & Daniel Cherqui & Charles Balabaud & Jessica Zucman-Rossi, 2013. "Correction: Corrigendum: High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions," Nature Communications, Nature, vol. 4(1), pages 1-1, December.
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