Myometrial oxidative stress drives MED12 mutations in leiomyoma.

ABSTRACT:

Background

More than 70% of leiomyomas (LM) harbor MED12 mutations, primarily in exon 2 at c.130-131(GG). The cause of MED12 mutations in myometrial cells remains largely unknown. We hypothesized that increased ROS promotes MED12 mutations in myometrial cells through the oxidation of guanine nucleotides followed by misrepair.

Methods

Genomic oxidative burden (8-OHdG) was evaluated in vitro and in vivo by immunohistochemistry. MED12 mutations were examined by Sanger sequencing and deep sequencing. Transcriptome examined by RNA-seq was performed in myometrium with and without LM, in primary myometrial cells treated with ROS. 8-OHdG mediated misrepair was analyzed by CRISPR/Cas9.

Results

Uteri with high LM burden had a significantly higher rate of MED12 mutations than ut

SUBMITTER: Li Y 

PROVIDER: S-EPMC9308324 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature