Oct 26, 2018

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

BioRxiv : the Preprint Server for Biology
Jitu W GeorgeJose M Teixeira

Abstract

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, Infinium MethylationEPIC array, and RNA-sequencing. Unsupervised clustering by DNA methylation segregated normal myometria from 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 fibr...Continue Reading

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Mentioned in this Paper

Transformation, Genetic
MED12 gene
DNA Methylation [PE]
HMGA2 Protein
HMGA2
HMGA1a Protein
Genes
Myometrial
Sequence Determinations, RNA
HMGA1

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