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.