Whole-genome methylation study of congenital lung malformations in children
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ABSTRACT:
PROVIDER: PRJNA730816 | ENA |
REPOSITORIES: ENA
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Project description: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.
2021-05-19 | GSE174625 | GEO
Project description:Background and objectivesThe 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.MethodsThe DNA extracted from resected congenital lung malformations and control lung tissue was screened using Illumina MethylationEPIC arrays. Comparisons 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. Moreover, each malformed sample was pairwise compared with its respective control. All differentially methylated regions (DMRs) with an adjusted p-value <0,05 were studied.ResultsEvery 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.ConclusionsMethylation anomalies already described in lung tumors and also shared by the PPB were found in congenital lung malformations, regardless the histology. The presence of methylation abnormalities is suggestive of a correlation between congenital lung malformations and some step of malignant transformation.
| S-EPMC8273538 | biostudies-literature
Project description:The purpose of this study was to identify gene expression changes associated with congenital lung malformations.
2018-01-23 | GSE100442 | GEO
Project description:To explore the long non-coding RNA (lncRNA) expression pattern of congenital lung malformations on a genome-wide scale and investigate their potential biological function in four types of congenital lung malformations.
2021-12-07 | GSE179404 | GEO
Project description:We used Affymetrix CytoScan750K array to detect the pathogenic copy number variations in 7 Chinese children with congenital heart disease
2021-10-01 | E-MTAB-8315 | biostudies-arrayexpress
Project description:Congenital biliary dilatation (CBD) is a relatively rare biliary tract disease. It is a prevalent congenital biliary disease in children. CBD mainly affects in infants and children, with a higher prevalence in females. To investigate the DNA methylation patterns in children with CBD and in healthy children, we performed a comparative analysis of the genome‐wide DNA methylation profiles of whole blood samples from patients with CBD child and from healthy children using the Illumina Infinium Human Methylation 850k BeadChip. Bioinformatics statistical analysis revealed that 5,863 genes with differential DNA methylation between the two groups correlated to a total of 24,230 methylated sites.Of these differential methylation sites, 831,3 were hypermethylated and 15,917 were hypomethylated in comparison to the methylation status of those sites in the control samples. Differentially methylated regions (DMRs) between the CBD cases and the control group was significant difference in DMR_1~DMR_54. Furthermore, T cell receptor signaling pathways represented accounted for an important percentage of the differentially methylated genes. Abnormalities in the DNA methylation pattern identified in the peripheral blood of CBD patients may play an important role in the development of CBD and warrant further investigation.
2025-08-22 | GSE275555 | GEO
Project description:The application of second-generation sequencing in congenital pulmonary airway malformations
| PRJNA787785 | ENA
Project description:Maternal dietary insufficiencies can reshape the offspring epigenome during gestation, contributing to birth defects and developmental disorders. Vitamin C (VitC) is a critical co-factor for Ten-Eleven-Translocation (TET) DNA demethylases, but the impact of its deficiency on embryonic development remains unclear. Here, we show that insufficient maternal VitC combined with genetic susceptibility can give rise to congenital malformations, including neural tube defects (NTDs), through dysregulation of DNA methylation. We previously reported NTDs in Tet1 knockout (KO) mice at low penetrance in C57BL/6J (B6) congenic inbred strains, but at two- to three-fold higher rates when outbred or highly backcrossed (incipient congenic) on a 129S6.B6 background. Similarly, maternal VitC deficiency in L-gulonolactone oxidase (Gulo) KO mice, which like humans are unable to synthesize VitC, resulted in highly penetrant congenital malformations in non-inbred mice, during a vulnerable window coinciding with gastrulation. DNA hypermethylation is a signature of VitC-deprived 129S6.B6-Gulo-/- embryonic headfold tissues, being absent in B6 embryos which are grossly normal. In outbred Gulo-/- embryonic brains, genomic regions harboring hypermethylation – hallmarks of TET dysfunction - increased with the severity of embryonic pathologies. A moderate reduction in VitC status is sufficient to induce hypermethylated regions and cause NTDs. Severe embryonic defects in VitC-deprived embryos can be rescued by timely re-supplementation of VitC at the onset of gastrulation, which normalized DNA methylation at most loci. Our results suggest that promoting timely VitC supplementation by at-risk pregnant mothers may prevent many birth defects currently refractory to folic acid supplementation and enhance the “health-span” of future generations.
2025-06-25 | GSE295922 | GEO
Project description:Maternal dietary insufficiencies can reshape the offspring epigenome during gestation, contributing to birth defects and developmental disorders. Vitamin C (VitC) is a critical co-factor for Ten-Eleven-Translocation (TET) DNA demethylases, but the impact of its deficiency on embryonic development remains unclear. Here, we show that insufficient maternal VitC combined with genetic susceptibility can give rise to congenital malformations, including neural tube defects (NTDs), through dysregulation of DNA methylation. We previously reported NTDs in Tet1 knockout (KO) mice at low penetrance in C57BL/6J (B6) congenic inbred strains, but at two- to three-fold higher rates when outbred or highly backcrossed (incipient congenic) on a 129S6.B6 background. Similarly, maternal VitC deficiency in L-gulonolactone oxidase (Gulo) KO mice, which like humans are unable to synthesize VitC, resulted in highly penetrant congenital malformations in non-inbred mice, during a vulnerable window coinciding with gastrulation. DNA hypermethylation is a signature of VitC-deprived 129S6.B6-Gulo-/- embryonic headfold tissues, being absent in B6 embryos which are grossly normal. In outbred Gulo-/- embryonic brains, genomic regions harboring hypermethylation – hallmarks of TET dysfunction - increased with the severity of embryonic pathologies. A moderate reduction in VitC status is sufficient to induce hypermethylated regions and cause NTDs. Severe embryonic defects in VitC-deprived embryos can be rescued by timely re-supplementation of VitC at the onset of gastrulation, which normalized DNA methylation at most loci. Our results suggest that promoting timely VitC supplementation by at-risk pregnant mothers may prevent many birth defects currently refractory to folic acid supplementation and enhance the “health-span” of future generations.
2025-06-25 | GSE295921 | GEO
Project description:<p>We report a study of large rare, copy number variants (CNVs) in 192 patients with renal hypodysplasia (RHD). Congenital malformations of the kidney and urinary tract are present in 3 to 7 per 1,000 births, accounting for 16% of birth defects. These malformations account for 40-50% of pediatric and 7% of adult end-stage renal disease worldwide. Among these malformations, RHD represents a severe forms of disease with profound impact on long-term renal survival. We found that a significant fraction of RHD patients have a molecular diagnosis attributable to a genomic disorder, suggesting kidney malformations as a sentinel manifestation of pathogenic genomic imbalances.</p>
| phs000565.v1.p1 | EGA