A novel SERPINE1-FOSB fusion gene in pseudomyogenic hemangioendothelioma results in activation of intact FOSB and the PI3K-AKT-mTOR signaling pathway and responsiveness to sirolimus

J Dermatol. 2021 Dec;48(12):1900-1906. doi: 10.1111/1346-8138.16158. Epub 2021 Sep 27.

Abstract

Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare disease that affects mainly the young and more men than women. PHE are multicentric, locally aggressive, have low metastatic potential, and affect multiple tissue planes. Genetic aberrations are frequently detected in PHE and may play important roles in the occurrence, development, and treatment of this disease. In this study, we report a case of PHE with a novel SERPINE1-FOSB fusion gene. The fusion introduced a strong promoter near the coding region of FOSB, resulting in overexpression of intact FOSB. Immunohistochemical analysis showed overexpression of pAKT and mTOR in tumor cells, suggesting activation of the PI3K-AKT-mTOR signaling pathway. The patient responded well to targeted therapy with sirolimus, an mTOR inhibitor. Our study correlated dysregulation of a specific signaling pathway and the effectiveness of a targeted therapy to a specific genetic aberration. This information may be useful for future investigations of targeted therapeutics and provide a potential predictive biomarker for therapeutic effectiveness in PHE cases.

Keywords: FOSB; PI3K-AKT-mTOR signaling pathway; SERPINE1-FOSB fusion; pseudomyogenic hemangioendothelioma; sirolimus.

Publication types

  • Case Reports

MeSH terms

  • Female
  • Hemangioendothelioma* / drug therapy
  • Hemangioendothelioma* / genetics
  • Humans
  • Male
  • Phosphatidylinositol 3-Kinases* / genetics
  • Plasminogen Activator Inhibitor 1
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Signal Transduction / genetics
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / genetics

Substances

  • FOSB protein, human
  • Plasminogen Activator Inhibitor 1
  • Proto-Oncogene Proteins c-fos
  • SERPINE1 protein, human
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Sirolimus