Open Access

Somatic driver mutations in endometriosis as possible regulators of fibrogenesis (Review)

  • Authors:
    • Hiroshi Kobayashi
  • View Affiliations

  • Published online on: May 13, 2019     https://doi.org/10.3892/wasj.2019.12
  • Pages: 105-112
  • Copyright: © Kobayashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of this review article was to assess the potential link between somatic driver mutations in endometriosis and the pathogenesis of fibrotic processes in other organ systems. This review presents the results of a PubMed literature search for publications dealing with the association between the endometriosis susceptibility driver gene mutations and pathological gene alterations related to fibrosis in the liver, kidney and lung. Genetic studies have demonstrated that endometriosis has somatic mutations in driver genes, including AT-rich interaction domain 1A (ARID1A), phosphatase and tensin homolog (PTEN), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), KRAS, tumor protein P53 (TP53), P16 or B-Raf proto-oncogene, serine/threonine kinase (BRAF), directly related to neoplasms. Tissue injury and repair induce inflammation and oxidative stress, which induces (epi)genetic DNA damage and mutations, promotes epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT) through the induction of fibrogenic signaling pathways regulated by transforming growth factor (TGF)-β/Smad and these driver genes, resulting in α-smooth muscle actin (α-SMA) and collagen production and increased cellular contractility, leading to increased smooth muscle metaplasia (SMM) and fibrosis. Elevated levels of reactive oxygen species may lead to increased damage to DNA and may induce cell cycle arrest accompanied by the acquisition of replication stress, senescence-associated characteristics and carcinogenesis, at least to a certain extent. This process may be a major hallmark of fibrogenesis of the liver, kidney and lung. Given that somatic driver mutations occur frequently in benign endometriosis and the physiologically normal endometrium, there may be at least 2 distinct phases of epigenetic and genetic modifications in endometriosis: The initial wave of hemoglobin-induced oxidative stress and (epi)genetic DNA damages and mutations would be followed by the second big wave of cellular senescence, fibrogenesis and finally, carcinogenesis. Thus, it can be concluded that endometriosis may represent a hemorrhage-induced fibrotic and low-grade pre-neoplastic lesion that may be a precursor lesion of a subset of malignant transformation.

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Copy and paste a formatted citation
APA
Kobayashi, H. (2019). Somatic driver mutations in endometriosis as possible regulators of fibrogenesis (Review). World Academy of Sciences Journal, 1, 105-112. https://doi.org/10.3892/wasj.2019.12
MLA
Kobayashi, H."Somatic driver mutations in endometriosis as possible regulators of fibrogenesis (Review)". World Academy of Sciences Journal 1.3 (2019): 105-112.
Chicago
Kobayashi, H."Somatic driver mutations in endometriosis as possible regulators of fibrogenesis (Review)". World Academy of Sciences Journal 1, no. 3 (2019): 105-112. https://doi.org/10.3892/wasj.2019.12