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Genetics and Genomics of Uterine Fibroids

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Uterine Fibroids and Adenomyosis

Part of the book series: Comprehensive Gynecology and Obstetrics ((CGO))

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Abstract

Uterine fibroids are benign smooth muscle tumors of monoclonal origin that arise from the uterus. African-American women have a higher risk of developing the disease than do Caucasian women, and a family history of uterine fibroids is a risk factor for their development. The relative risk for uterine fibroids is significantly higher in monozygotic twins than in dizygotic twins, suggesting a correlation of the disease susceptibility with the patient’s genetic background. Chromosomal abnormalities are observed in approximately 40% of cases, where nonrandom and tumor-specific chromosomal abnormalities caused by chromosomal rearrangements affect alterations in the driver genes of uterine fibroids, such as high-mobility group AT-hook 2 (HMGA2) overexpression. Hereditary leiomyomatosis and renal cell cancer are caused by biallelic inactivation of the fumarase hydratase (FH) gene. Alport syndrome associated with diffuse leiomyomatosis is caused by deletions of collagen type IV alpha 5 chain (COL4A5) and alpha 6 chain (COL4A6). Somatic alterations of these genes are also observed in non-syndromic uterine fibroids. Whole-genome sequencing (WGS) revealed that approximately 70% of uterine fibroids have somatic mutations of Mediator complex 12 (MED12), which is the most frequently observed driver gene alteration in these tumors. Through WGS, uterine fibroids have been categorized into at least four subgroups according to the types of driver gene alterations: MED12 mutation, HMGA2 overexpression, biallelic FH inactivation, and COL4A5 and COL4A6 deletions. Each alteration is mutually exclusive in the fibroid nodule. In addition, the role of microRNAs in the development of uterine fibroids is extensively examined.

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Authors and Affiliations

  1. Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

    Hiroshi Ishikawa M.D., Ph.D. & Makio Shozu M.D, Ph.D.

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  1. Hiroshi Ishikawa M.D., Ph.D.
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Correspondence to Hiroshi Ishikawa M.D., Ph.D. .

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  1. Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan

    Norihiro Sugino

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Ishikawa, H., Shozu, M. (2018). Genetics and Genomics of Uterine Fibroids. In: Sugino, N. (eds) Uterine Fibroids and Adenomyosis. Comprehensive Gynecology and Obstetrics. Springer, Singapore. https://doi.org/10.1007/978-981-10-7167-6_2

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