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LHX6 promoter hypermethylation in oncological pediatric patients conceived by IVF

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Author(s):
Dangoni, Gustavo Dib ; Barbosa Teixeira, Anne Caroline ; Camargo Vince, Carolina Sgarioni ; Novak, Estela Maria ; Gimenez, Thamiris Magalhaes ; Maschietto, Mariana ; Odone Filho, Vicente ; Victorino Krepischi, Ana Cristina
Total Authors: 8
Document type: Journal article
Source: JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE; v. 14, n. 1, p. 6-pg., 2022-09-26.
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. (AU)

FAPESP's process: 18/21047-9 - Childhood cancer: genetic predisposition and mechanisms of origin
Grantee:Ana Cristina Victorino Krepischi
Support Opportunities: Regular Research Grants
FAPESP's process: 18/05961-2 - Identification of genetic variants related to cancer predisposition in cohort of patients with embryonal tumors or pediatric tumors and additional clinical signs
Grantee:Anne Caroline Barbosa Teixeira
Support Opportunities: Scholarships in Brazil - Post-Doctoral