promoter hypermethylation in oncological pediatric patients conceived by IVF.

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 fertilization (IVF), and birth defects, 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 , a transcription factor involved in the forebrain development and interneuron migration during embryogenesis. An additional control group was included to verify the methylation status in children with similar cancers who were not conceived by ART. The higher 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 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 promoter hypermethylation for tumorigenesis.