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LHX6 promoter hypermethylation in oncological pediatric patients conceived by IVF
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  • Gustavo Dangoni,
  • Anne Caroline Teixeira,
  • Carolina Vince,
  • Estela Novak,
  • Mariana Maschietto,
  • Vicente Odone,
  • Ana Krepischi
Gustavo Dangoni
Universidade de Sao Paulo Instituto de Biociencias

Corresponding Author:gustavodib@usp.br

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Anne Caroline Teixeira
Universidade de Sao Paulo Instituto de Biociencias
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Carolina Vince
ITACI - Instituto de Tratamento do Câncer Infantil
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Estela Novak
ITACI - Instituto de Tratamento do Câncer Infantil
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Mariana Maschietto
Boldrini Children's Hospital
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Vicente Odone
ITACI - Instituto de Tratamento do Câncer Infantil
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Ana Krepischi
Universidade de Sao Paulo Instituto de Biociencias
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Abstract

Background: The multifactorial etiology of pediatric cancer is poorly understood. Environmental factors occurring during embryogenesis can disrupt epigenetic signaling, resulting in several diseases after birth, including cancer. Studies have reported associations between assisted reproductive technologies, such as in vitro fertilization (IVF), and birth defects, imprinting disorders and other perinatal adverse events. IVF can result in methylation changes in the offspring and a link with pediatric cancer has been suggested. Procedure: In this study, we investigated the peripheral blood methylomes of eleven patients conceived by IVF who developed cancer in childhood. Methylation data of patients and paired sex/aged controls were obtained using the Infinium MethylationEPIC Kit (Illumina), which interrogates ~850K CpG sites. Results: We identified 43 differentially methylated regions (DMR) in patients, 26 of them hypermethylated, and 17 hypomethylated. The most significant DMR was a hypermethylated genomic segment located in the promoter region of LHX6, a transcription factor involved in embryogenesis. Conclusion: The hypermethylation of the LHX6 promoter region, that was identified in this study, has been found in several cancer types. Further studies are required to evaluate the potential relevance of LHX6 promoter hypermethylation for tumorigenesis in children conceived by IVF.