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Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease

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Abstract

Purpose

Despite the numerous studies on the factors involved in the genesis and growth of uterine leiomyomas, the pathogenesis of these tumors remains unknown. Intrinsic abnormalities of the myometrium, abnormal myometrial receptors for estrogen, and hormonal changes or altered responses to ischemic damage during the menstrual period may be responsible for the initiation of (epi)genetic changes found in these tumors. Considering these elements, we aimed to offer an overview about epigenetic and genetic landscape of uterine leiomyomas.

Methods

Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases.

Results

Several studies showed that leiomyomas have a monoclonal origin. Accumulating evidence converges on the risk factors and mechanisms of tumorigenesis: the translocation t (12;14) and deletion of 7q were found in the highest percentages of recurrence; dysregulation of the HMGA2 gene has been mapped within the critical 12q14–q15 locus. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has been poorly explored. The growth factors with mitogenic activity, such as transforming growth factor-β3, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I are elevated in fibroids and may have a role as effectors of the tumor promotion.

Conclusion

The new clues on genetics and epigenetics, as well as about the growth factors that control normal and pathological myometrial cellular biology may be of great help for the development of new effective and less invasive therapeutic strategies in the near future.

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Authors and Affiliations

  1. Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University of Messina, Via C. Valeria 1, 98125, Messina, Italy

    Antonio Simone Laganà, Onofrio Triolo & Salvatore Giovanni Vitale

  2. Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy

    Daniele Vergara

  3. Laboratory of Clinical Proteomic, “Giovanni Paolo II” Hospital, ASL Lecce, Lecce, Italy

    Daniele Vergara

  4. Department of Obstetrics and Gynecology, University of Perugia, Perugia, Italy

    Alessandro Favilli & Sandro Gerli

  5. Unit of Psychodiagnostics and Clinical Psychology, University of Catania, Catania, Italy

    Valentina Lucia La Rosa

  6. Division of Experimental Endoscopic Surgery, Imaging, Technology and Minimally Invasive Therapy, Department of Obstetrics and Gynecology, Vito Fazzi Hospital, Lecce, Italy

    Andrea Tinelli

  7. Department of Woman and Child Health, University of Padua, Padua, Italy

    Marco Noventa & Amerigo Vitagliano

  8. Division of Obstetrics and Gynecology, Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy

    Agnese Maria Chiara Rapisarda

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  1. Antonio Simone Laganà
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ASL, DV, AF, AT: manuscript writing, VLLR, MN, AV, AMCR: literature screening and data selection, SG, OT: manuscript editing, SGV: project supervision and final approval.

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Correspondence to Antonio Simone Laganà.

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Laganà, A.S., Vergara, D., Favilli, A. et al. Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease. Arch Gynecol Obstet 296, 855–867 (2017). https://doi.org/10.1007/s00404-017-4515-5

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