Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations

Somatic mutations in Mediator complex subunit 12 (MED12m) have been
reported as a biomarker of uterine fibroids
(UFs).  However, the role of MED12m is still unclear in
the pathogenesis of UFs.  Therefore, we investigated the
differences in DNA methylome, transcriptome, and histological features
between MED12m-positive and -negative UFs.  DNA methylomes and
transcriptomes were obtained from MED12m-positive and -negative UFs and
myometrium, and hierarchically
clustered.  Differentially expressed genes in comparison
with the myometrium and co-expressed genes detected by weighted gene
co-expression network analysis were subjected to gene ontology enrichment
analyses.  The amounts of collagen fibers and the number
of blood vessels and smooth muscle cells were histologically
evaluated. Hierarchical clustering based on DNA methylation
clearly separated the myometrium, MED12m-positive, and MED12m-negative
UFs.  MED12m-positive UFs showed the increased
activities of extracellular matrix formation, whereas MED12m-negative UFs
had the increased angiogenic activities and smooth muscle cell
proliferation. The MED12m-positive and -negative UFs had
different DNA methylation, gene expression, and histological
features.  The MED12m-positive UFs form the tumor with a
rich extracellular matrix and poor blood vessels and smooth muscle cells
compared to the MED12m-negative UFs, suggesting MED12 mutations affect the
tissue composition of UFs.