Pathogenomics of Uterine Fibroids Development

We review recent studies dealing with the molecular genetics and basic results of omics analysis of uterine leiomyoma (LM)-a common benign muscle tumor of the uterus. Whole genome studies of LM resulted in the discovery of many new gene nets and biological pathways, including its origin, transcriptomic, and epigenetic profiles, as well as the impact of the inter-cell matrix in LM growth and involvement of microRNA in its regulation. New data on somatic cell mutations ultimately involved in the origin, distribution and growth of LM are reviewed. Putative identification of LM progenitor SC (stem cells) giving rise to maternal fibroid nodes and junctional zones provide a new clue for hypotheses on the pathogenomics of LM. The reviewed data are consistent with at least two different but probably intimately interacted molecular mechanisms of LM. One of them (the genetic hypothesis) is focused primarily on the <i>MED12</i> gene mutations and suggests its onset in the side population of embryonic myoblasts of the female reproductive system, which later gave rise to multiple small and medium fibroids. The single and usually large-size fibroids are induced by predominantly epigenetic disorders in LM SC, provoked by enhanced expression of the <i>HMGA2</i> gene caused by its hypomethylation and epigenetic deregulation enhanced by hypoxia, muscle tension, or chromosome instability/aberrations. The pathogenomics of both genetic and epigenetic programs of LM with many peculiarities at the beginning later became rather similar and partly overlapped due to the proximity of their gene nets and epigenetic landscape. Pathogenomic studies of LM open ways for elaboration of novel strategies of prevention and treatment of this common disease.