Scholarlink

<p>Erdheim–Chester Disease (ECD) is a rare histiocytosis characterized by a wide spectrum of clinical manifestations. Although somatic mutations have been involved in ECD, its etiology remains poorly understood. This study aimed to identify novel molecular mechanisms involved in ECD through the first integrated methylome and transcriptome analysis. Peripheral blood samples were collected from 137 ECD patients and 410 controls. Genome-wide DNA methylation and transcriptome analyses were performed, followed by functional in silico studies using different online bioinformatics tools. Subsequently, methylome and transcriptome data were integrated, and a drug repurposing approach was undertaken. Our results revealed 2511 differentially methylated positions and 1484 differentially expressed genes associated with ECD. The integrative analysis identified 46 alterations in DNA methylation patterns that regulate the expression levels of 29 altered genes in ECD patients, highlighting key genes involved in immune response and tumorigenesis. Remarkably, our results identified B cells and NF-kB signaling pathway as novel contributors of ECD pathogenesis. Finally, the drug repurposing analysis identified potential therapeutic options for ECD patients. In conclusion, this study represents an important advance in understanding the molecular basis of ECD, proposing novel cell types and pathways involved in ECD pathogenesis and suggesting new avenues for clinical management.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Unraveling the molecular landscape of Erdheim–Chester disease: new insights from methylome and transcriptome integration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月21日

查看全文
  • Miriam Cerván-Martín,
  • Francesco Pegoraro,
  • Javier Martínez-López,
  • Inmaculada Rodriguez-Martin,
  • Ana Márquez,
  • Lourdes Ortiz-Fernández,
  • Marialbert Acosta-Herrera,
  • Martin Kerick,
  • Eduardo Andrés-León,
  • Francesco Catamerò,
  • Matthias Papo,
  • Fleur Cohen-Aubart,
  • Zahir Amoura,
  • Julien Haroche,
  • Augusto Vaglio,
  • Javier Martín

摘要

Erdheim–Chester Disease (ECD) is a rare histiocytosis characterized by a wide spectrum of clinical manifestations. Although somatic mutations have been involved in ECD, its etiology remains poorly understood. This study aimed to identify novel molecular mechanisms involved in ECD through the first integrated methylome and transcriptome analysis. Peripheral blood samples were collected from 137 ECD patients and 410 controls. Genome-wide DNA methylation and transcriptome analyses were performed, followed by functional in silico studies using different online bioinformatics tools. Subsequently, methylome and transcriptome data were integrated, and a drug repurposing approach was undertaken. Our results revealed 2511 differentially methylated positions and 1484 differentially expressed genes associated with ECD. The integrative analysis identified 46 alterations in DNA methylation patterns that regulate the expression levels of 29 altered genes in ECD patients, highlighting key genes involved in immune response and tumorigenesis. Remarkably, our results identified B cells and NF-kB signaling pathway as novel contributors of ECD pathogenesis. Finally, the drug repurposing analysis identified potential therapeutic options for ECD patients. In conclusion, this study represents an important advance in understanding the molecular basis of ECD, proposing novel cell types and pathways involved in ECD pathogenesis and suggesting new avenues for clinical management.