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Integrated epigenome, exome and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids [DNA methylation]

ABSTRACT: Integrated epigenome, exome and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids [DNA methylation]

PROVIDER: PRJNA494715 | ENA |

REPOSITORIES: ENA

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Integrated epigenome, exome and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids

Project description:Uterine fibroids are benign myometrial smooth muscle tumors of unknown etiology that when symptomatic are the most common indication for hysterectomy in the USA. We conducted an integrated analysis of fibroids and adjacent normal myometria by whole exome sequencing, DNA methylation (Human Methylation EPIC) array, and RNA-sequencing. Unsupervised clustering by DNA methylation segregated normal myometria and fibroids, and further separated the fibroids into subtypes marked by MED12 mutation, HMGA2 activation (HMGA2hi) and HMGA1 activation (HMGA1hi). Upregulation of HMGA2 expression in HMGA2hi fibroids did not always appear to be dependent on translocation, as has been historically described, and was associated with hypomethylation in the HMGA2 gene body. Furthermore, we found that expression of HOXA13 was highly upregulated in fibroids and that overexpression of HOXA13 in a myometrial cell line induced expression of genes classically associated with uterine fibroids. Transcriptome analyses of the most differentially expressed genes between cervix and myometrium also showed that uterine fibroids and normal cervix clustered together and apart from normal myometria. Together, our integrated analysis shows a role for epigenetic modification in fibroid biology and strongly suggests that homeotic transformation of myometrium cells to a more cervical phenotype is important for the etiology of the disease.

2019-08-07 | GSE135446 | GEO

Integrated epigenome, exome and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids [DNA methylation]

2018-10-05 | GSE120854 | GEO

Integrated epigenome, exome and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids

Project description:Integrated epigenome, exome and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids

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Integrated Epigenome, Exome, and Transcriptome Analyses Reveal Molecular Subtypes and Homeotic Transformation in Uterine Fibroids.

Project description:Uterine fibroids are benign myometrial smooth muscle tumors of unknown etiology that, when symptomatic, are the most common indication for hysterectomy in the United States. Unsupervised clustering of results from DNA methylation analyses segregates normal myometrium from fibroids and further segregates the fibroids into subtypes characterized by MED12 mutation or activation of either HMGA2 or HMGA1 expression. Upregulation of HMGA2 expression does not always appear to be dependent on translocation but is associated with hypomethylation in the HMGA2 gene body. HOXA13 expression is upregulated in fibroids and correlates with expression of typical uterine fibroid genes. Significant overlap of differentially expressed genes is observed between cervical stroma and uterine fibroids compared with normal myometrium. These analyses show a possible role of DNA methylation in fibroid biology and suggest that homeotic transformation of myometrial cells to a more cervical stroma phenotype could be an important mechanism for etiology of the disease.

| S-EPMC6956710 | biostudies-literature

Gut microbiota: uterine fibroids patients vs. healthy control

Project description:Gut microbial profiling of uterine fibroids (UFs) patients comparing control subjects. The gut microbiota was examined by 16S rRNA quantitative arrays and bioinformatics analysis. The goal was to reveal alterations in the gut microbiome of uterine fibroids patients.

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Transcriptome of human myometrial stem cells in the context of uterine fibroids

Project description:Our study represents a new strategy for identifying drivers and risk factors of uterine fibroids (F) by identifying genes and pathways differentially regulated in myometrial stem cells (SCs) isolated from myometrium without fibroids (MyoN) and from myometrium adjacent to uterine fibroids (MyoF) using RNA-seq approach. Moreover, we will perform the comparison analysis of the transcriptome between MyoF SCs and fibroid SCs to identify differentially expressed genes.

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Transcription profiling of human mayometrium and uterine fibroids with normal and non-normal karyotypes

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