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LHX6 promoter hypermethylation in oncological pediatric patients conceived by IVF

Published online by Cambridge University Press:  26 September 2022

Gustavo Dib Dangoni Open the ORCID record for Gustavo Dib Dangoni [Opens in a new window] ,
Anne Caroline Barbosa Teixeira ,
Carolina Sgarioni Camargo Vince ,
Estela Maria Novak ,
Thamiris Magalhães Gimenez ,
Mariana Maschietto ,
Vicente Odone Filho  and
Ana Cristina Victorino Krepischi Open the ORCID record for Ana Cristina Victorino Krepischi [Opens in a new window]
Gustavo Dib Dangoni
Affiliation:
Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil
Anne Caroline Barbosa Teixeira
Affiliation:
Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil
Carolina Sgarioni Camargo Vince
Affiliation:
Institute for the Treatment of Childhood Cancer (ITACI) – Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
Estela Maria Novak
Affiliation:
Institute for the Treatment of Childhood Cancer (ITACI) – Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
Thamiris Magalhães Gimenez
Affiliation:
Institute for the Treatment of Childhood Cancer (ITACI) – Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
Mariana Maschietto
Affiliation:
Research Center, Boldrini Children’s Hospital, Campinas, SP, Brazil
Vicente Odone Filho
Affiliation:
Institute for the Treatment of Childhood Cancer (ITACI) – Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
Ana Cristina Victorino Krepischi*
Affiliation:
Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil
*
Address for correspondence: Ana Cristina Victorino Krepischi. Institute of Biosciences - University of São Paulo - Rua do Matão 277, 05508-090, São Paulo, SP, Brazil. Email: ana.krepischi@ib.usp.br
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Abstract

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. Associations between assisted reproductive technologies (ART), such as in vitro fertilization (IVF), and birth defects, imprinting disorders and other perinatal adverse events have been reported. IVF can result in methylation changes in the offspring, and a link with pediatric cancer has been suggested. In this study, we investigated the peripheral blood methylomes of 11 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). We identified 25 differentially methylated regions (DMRs), 17 of them hypermethylated, and 8 hypomethylated in patients. The most significant DMR was a hypermethylated genomic segment located in the promoter region of LHX6, a transcription factor involved in the forebrain development and interneuron migration during embryogenesis. An additional control group was included to verify the LHX6 methylation status in children with similar cancers who were not conceived by ART. The higher LHX6 methylation levels in IVF patients compared to both control groups (healthy children and children conceived naturally who developed similar pediatric cancers), suggested that hypermethylation at the LHX6 promoter could be due to the IVF process and not secondary to the cancer itself. Further studies are required to evaluate this association and the potential role of LHX6 promoter hypermethylation for tumorigenesis.

Keywords

Pediatric cancerepigeneticsDNA methylationARTIVF
Type
Brief Reports
Information
Journal of Developmental Origins of Health and Disease , Volume 14 , Issue 1 , February 2023 , pp. 140 - 145
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Copyright
© The Author(s), 2022. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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Footnotes

Vicente Odone Filho and Ana Cristina Victorino Krepischi equally contribution last authors.

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