International Center for Cancer Vaccine Science (ICCVS), University of Gdansk, Gdańsk, Poland.
Department of Basic Medical Sciences, Faculty of Medicine, The Hashemite University, Zarqa, Jordan.
BMC Med Genomics. 2022 Jun 6;15(1):128. doi: 10.1186/s12920-022-01277-x.
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.
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.
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.
Gorham-Stout 病是一种罕见的疾病，其特征为血管增生和大量骨质破坏。文献中记载的 Gorham-Stout 综合征病例不足 400 例，我们进行了一项独特的研究，结合全基因组测序和 RNA-Seq 来探究该病例的基因组特征和差异表达途径，揭示了疾病的新的可能驱动因素和生物标志物。
我们报告了一例罕见病例，一名 45 岁白人女性患者左侧肱骨有明显骨质缺失，伴血管增生，诊断为 Gorham-Stout 病。全基因组测序分析显示，大片段结构 DNA 重排占主导地位。特别是染色体 7、12 和 20 上的重排可能导致疾病的发生，特别是涉及 ATG101 的基因融合，可能会影响巨自噬。对患者 RNA-seq 数据的研究揭示了 PI3K/AKT/mTOR 信号通路是 Gorham-Stout 病变组织中受影响最严重的信号级联。此外，通过 RNA-seq 表达数据的去卷积检测到 M2 巨噬细胞浸润，并通过免疫组织化学染色得到证实。
由于研究该罕见疾病的数量有限，因此 DNA 和 RNA 异常导致 Gorham-Stout 病的机制尚不清楚。我们的研究首次揭示了该疾病的这一方面，为新的可能治疗靶点提供了线索，并有助于 Gorham-Stout 病的临床病理诊断。
