Whole-genome methylation study of congenital lung malformations in children

The treatment of asymptomatic patients with congenital pulmonary malformations (CPMs) remains controversial, partially because the relationship between congenital lung malformations and malignancy is still undefined. Change in methylation pattern is a crucial event in human cancer, including lung cancer. We therefore studied all differentially methylated regions (DMRs) in a series of CPMs in an attempt to find methylation anomalies in genes already described in association with malignancy. The DNA extracted from resected congenital lung malformations and control lung tissue was screened using Illumina MethylationEPIC arrays. Comparison between the group of malformed samples or the malformed samples of same histology or each malformed sample and the controls, and between a pleuropulmonary blastoma (PPB) and controls were performed. All differentially methylated regions (DMRs) with an adjusted p value < 0,05 were studied. Every comparison highlighted a number of DMRs closed to genes involved either in cell proliferation or in embryonic development or included in the Cancer Gene Census. Their abnormal methylation had been already described in lung tumors. The presence of methylation abnormalities is suggestive of a correlation between congenital lung malformations and some step of malignant transformation. 29 total fresh-frozen paediatric lung samples: 8 healthy lung tissues, 1 Pleuropulmonary Blastoma sample, 20 Congenital Pulmonary Malformation tissues