LHX6 promoter hypermethylation in oncological pediatric patients conceived by IVF

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.