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BIRTH DEFECTS AND CHILDHOOD CANCER: A SHARED BIOLOGICAL PATHWAY FOR HIRSCHSPRUNG DISEASE AND HEPATOBLASTOMA DEVELOPMENT?
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  • Talita Aguiar*,
  • Anne Caroline Teixeira,
  • Juliana Sobral,
  • Silvia Souza Costa,
  • Marília Scliar,
  • Renata Hall-Nielsen,
  • Ana Regina Ramos,
  • Beatriz dos Santos,
  • Valentina Oliveira,
  • Ariane Backes,
  • Osvaldo Artigalás,
  • Isabela Cunha,
  • Carla Rosenberg,
  • Eugênia Valadares,
  • Raquel Pinto,
  • Ana Krepischi
Talita Aguiar*
Institute of Biosciences, University of Sao Paulo
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Anne Caroline Teixeira
Institute of Biosciences, University of Sao Paulo
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Juliana Sobral
Institute of Biosciences, University of Sao Paulo
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Silvia Souza Costa
Institute of Biosciences, University of Sao Paulo
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Marília Scliar
University of São Paulo
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Renata Hall-Nielsen
Benjamim Guimarães Foundation
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Ana Regina Ramos
Grupo Hospitalar Conceição
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Beatriz dos Santos
Grupo Hospitalar Conceição
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Valentina Oliveira
Grupo Hospitalar Conceição
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Ariane Backes
Grupo Hospitalar Conceição
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Osvaldo Artigalás
Grupo Hospitalar Conceição
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Isabela Cunha
Rede D’OR-São Luiz
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Carla Rosenberg
Institute of Biosciences, University of Sao Paulo
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Eugênia Valadares
Benjamim Guimarães Foundation
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Raquel Pinto
Grupo Hospitalar Conceição
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Ana Krepischi
Institute of Biosciences, University of Sao Paulo
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Abstract

Background: The association of birth defects and developmental alterations with pediatric cancer is a recognized long-standing global observation, although very few syndromes confer a high risk of hepatoblastoma development. Procedures: Here we describe the results of germline exome analysis of two syndromic patients with Hirschsprung disease who developed hepatoblastoma. Results: Germline variants of uncertain clinical significance (VUS) were disclosed in 28 genes that might be related to patients’ phenotypes. More importantly, germline VUS were detected in eight known cancer predisposition genes (APC, BRCA1, ERBB2, ERCC2, HRAS, ODC1, SERPINA6, and MCC). Additionally, our data disclosed two candidate genes with germline variants potentially contributing to the phenotype of these patients, namely, CEP164 and CYP1A1. The last one was the only gene presenting variants of uncertain significance in both patients. This gene encodes the most important xenobiotic-metabolizing enzyme of the placenta for which relevant inducible activity has been demonstrated throughout pregnancy. Conclusion: our data pointed out a set of genes that are enriched for pathways already related to cancer and developmental biology, suggesting they could have a broader role in cancer and congenital abnormalities. These results can help future studies to understand the biology of Hirschsprung disease and its association with hepatoblastoma.