Multiple Mutations in Exon-2 of Med-12 Identified in Uterine Leiomyomata

Uterine leiomyomata (UL), commonly known as uterine fibroids, are benign smooth muscle tumors of the myometrium. They cause pelvic pain, abnormal uterine bleeding, and infertility in women of reproductive age. The ovarian hormone estrogen is the main stimulator for the fibroid growth. The etiology is not yet clearly understood; however, UL are believed to be monoclonal tumors arising from a common progenitor cell. Chromosomal cytogenetic abnormalities have been demonstrated in 40-50% of the fibroids. The most frequent tumor specific genetic alterations in UL were identified in exon-2 of Mediator Complex Subunit 12 (MED-12).

In the present study, twenty-two multiple fibroids were evaluated both from the same uterus and from different uteri, of four women, for somatic mutations in hotspot region of MED-12. The tissue DNA of the UL's was isolated, amplified by PCR visualized on gel and sent for Sanger sequencing.

The results indicate several variants in exon-2 and flanking intronic regions, seven exonic variants and five intronic variants which provide evidence that multiple UL in the same uterus may not be clonal in origin.

This study indicates genetic heterogeneity. UL may not have a clonal origin, these exon-2 variants of MED-12 gene could be involved in UL progression.