Antonio Simone Laganà1, Daniele Vergara2,3, Alessandro Favilli4, Valentina Lucia La Rosa5, Andrea Tinelli6, Sandro Gerli4, Marco Noventa7, Amerigo Vitagliano7, Onofrio Triolo8, Agnese Maria Chiara Rapisarda9, Salvatore Giovanni Vitale8. 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. antlagana@unime.it. 2. Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy. 3. Laboratory of Clinical Proteomic, "Giovanni Paolo II" Hospital, ASL Lecce, Lecce, Italy. 4. Department of Obstetrics and Gynecology, University of Perugia, Perugia, Italy. 5. Unit of Psychodiagnostics and Clinical Psychology, University of Catania, Catania, Italy. 6. Division of Experimental Endoscopic Surgery, Imaging, Technology and Minimally Invasive Therapy, Department of Obstetrics and Gynecology, Vito Fazzi Hospital, Lecce, Italy. 7. Department of Woman and Child Health, University of Padua, Padua, Italy. 8. 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. 9. Division of Obstetrics and Gynecology, Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy.
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.
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.
Authors: María Cristina Carbajo-García; Lucia de Miguel-Gómez; Elena Juárez-Barber; Alexandra Trelis; Javier Monleón; Antonio Pellicer; James M Flanagan; Hortensia Ferrero Journal: Biomedicines Date: 2022-05-30