Gorham-Stout case report: a multi-omic analysis reveals recurrent fusions as new potential drivers of the disease

Marcos Yébenes Mayordomo, Sofian Al Shboul, Maria Gómez-herranz, Asim Azfer, Alison Meynert, Donald Salter, Larry Hayward, Anca Oniscu, James T. Patton, Ted Hupp, Mark J. Arends, Javier Antonio Alfaro

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

BACKGROUND: Gorham-Stout disease is a rare condition characterized by vascular proliferation and the massive destruction of bone tissue. With less than 400 cases in the literature of Gorham-Stout syndrome, we performed a unique study combining whole-genome sequencing and RNA-Seq to probe the genomic features and differentially expressed pathways of a presented case, revealing new possible drivers and biomarkers of the disease.

CASE PRESENTATION: We present a case report of a white 45-year-old female patient with marked bone loss of the left humerus associated with vascular proliferation, diagnosed with Gorham-Stout disease. The analysis of whole-genome sequencing showed a dominance of large structural DNA rearrangements. Particularly, rearrangements in chromosomes seven, twelve, and twenty could contribute to the development of the disease, especially a gene fusion involving ATG101 that could affect macroautophagy. The study of RNA-sequencing data from the patient uncovered the PI3K/AKT/mTOR pathway as the most affected signaling cascade in the Gorham-Stout lesional tissue. Furthermore, M2 macrophage infiltration was detected using immunohistochemical staining and confirmed by deconvolution of the RNA-seq expression data.

CONCLUSIONS: The way that DNA and RNA aberrations lead to Gorham-Stout disease is poorly understood due to the limited number of studies focusing on this rare disease. Our study provides the first glimpse into this facet of the disease, exposing new possible therapeutic targets and facilitating the clinicopathological diagnosis of Gorham-Stout disease.

Original languageEnglish
Pages (from-to)128
JournalJournal Title BMC Medical Genomics
Issue number1
Early online date6 Jun 2022
Publication statusPublished - 6 Jun 2022

Keywords / Materials (for Non-textual outputs)

  • Humans
  • Middle Aged
  • Osteolysis, Essential/complications
  • Phosphatidylinositol 3-Kinases
  • RNA


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