Detection of exon2-MED12 mutations in uterine leiomyomas from Syrian patients

Uterine leiomyomas (uLMs) are the most prevalent benign tumors of the female reproductive system. MED12 is one of the mediator complex subunits that has been implicated in uLMs pathogenesis. Somatic mutations in exon2-MED12 have been found in ~ 70% of uLMs. In this study, we investigated the status of exon2-MED12 in uLMs from Syrian patients. Sixteen leiomyomas from nine patients were assessed. Genomic DNA was isolated from tumors and exon2-MED12 was amplified by PCR and sequenced. Three specimens showed in frame point mutations consisted of missense substitutions in codon 44 (c.130). A novel insertion in codon 35 (c.103insG) was detected in one of the mutated cases and is expected to cause a frameshift in translation and an altered or truncated product. Some of the wild-type uLMs were collected from the same uteri that revealed mutations, which emphasizes the individuality of the uLM lesions and highlights the complexity of uLMs pathogenesis. The study is the first report from Syria on the topic and the second from the Arab world. It indicates genetic heterogeneity and independent clonal origin of the somatic mutations in exon2-MED12. In wild-type uLMs where exon2-MED12 mutations are absent, other players are in place and should be investigated.