Research Resource: Genome-Wide Profiling of Methylated Promoters in Endometriosis Reveals a Subtelomeric Location of Hypermethylation

Abstract

Several lines of evidence indicate that endometriosis could be partially due to selective epigenetic deregulations. Promoter hypermethylation of some key genes, such as progesterone receptor and aromatase, has been associated with the silencing of these genes and might contribute to the disease. However, it is unknown whether global alterations in DNA methylation patterns occur in endometriosis and to what extent they are involved in its pathogenesis. We conducted a whole-genome scanning of methylation status in more than 25,000 promoters, using methylated DNA immunoprecipitation with hybridization to promoter microarrays. We detailed the methylation profiles for each subtype of the disease (superficial endometriosis, endometriomas, and deep infiltrating endometriosis) and compared them with the profile obtained for the eutopic endometrium. In line with the current theory of the endometrial origin of endometriosis, the overall methylation profile was highly similar between the endometrium and the lesions. It showed promoter regions consistently hypomethylated or hypermethylated (more than 1.5-times, as compared with endometrium) and others specific to one given subtype. Albeit there was no systematic correlation between promoter methylation and expression of nearby genes, 35 genes had both methylation and expressional alterations in the lesions. These genes, reported here for the first time, might be of interest in the development of endometriosis. In addition, hypermethylated regions were located at the ends of the chromosomes, whereas hypomethylated regions were randomly distributed all along the chromosomes. We postulated that this original observation might participate to the chromosomal stability and protect the endometriotic lesion against malignancy.

Epigenetics in Endometriosis

“…However, it is unknown whether global alterations in DNA methylation patterns occur in endometriosis and to what extent they are involved in its pathogenesis. A whole-genome scanning of CpG methylation status in more than 25,000 promoters has been conducted previously [54]. The results showed highly similar methylation profiles between endometrium and endometriotic lesions.…”

Molecular-genetic background of endometriosis: diagnostic potential of heritable and expressed factors

“…За последние годы в англоязычной литературе появились десятки публикаций, описывающих разницу в экспрессии факторов регуляции иммунного статуса [17], апоптотической активности [18], метастатического потенциала [19], наблюдае-мую между эктопическим и эутопическим эпи-телием. Ряд публикаций посвящен исследова-нию разницы эпигенетических особенностей: метилированию [20,21], экспрессии регуля-торных молекул РНк [22] и др. Результаты этих исследований носят описательный характер и плохо сопоставимы.…”

Markers of Adult Endometriosis Detectable in Adolescence

“…With goal this in mind, our team obtained robust results demonstrating specific gene expression and methylation profiles proper to each category of the endometriotic disease. [44][45][46] The following conclusions may be drawn from these points: (1) the existence of predisposing factors in endometriosis argues for early screening in young patients with a familial history of endometriosis; (2) large-scale genetic studies appear promising for calculating risk scores for clinical classes of endometriosis, provided the phenotype is clearly and precisely defined; and (3) future studies should focus on noninvasive diagnosis of endometriosis in selected populations. These studies should focus especially on adolescents with high-risk characteristics (severe dysmenorrhea, dysmenorrhea resistant to NSAID therapy and requiring noncontraceptive prescription of OC, positive familial history of endometriosis, etc.).…”