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<p>Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Cystic GBM is a phenotypic subset requiring distinct clinical management. This study aimed to comprehensively assess the genomic landscape of cystic GBM. GBM, <i>IDH</i> wild-type patients with available next-generation sequencing and presurgical brain MRI data were evaluated for cysts by neuroimaging specialists and a senior neuroradiologist. Patients with incomplete radiological or histopathological data, treatment-related cysts, or indeterminate cyst status were excluded. We used logistic regression to assess the association of cystic GBM with demographic variables and the top 24 altered genes. We employed Cox regression to analyze the association of cystic GBM with survival. Among 374 eligible patients, we identified 111 (30%) with cystic GBM and 263 (70%) with non-cystic GBM. Multivariable logistic regression revealed the association of cystic GBM with alterations of the <i>KDR</i> (OR 8.75 [1.77–43.3], <i>p</i> = 0.038), <i>RB1</i> (OR 5.12 [2.58–10.1], <i>p</i> = 0.008), <i>TP53</i> (OR 2.72 [1.67–4.43], <i>p</i> = 0.008), <i>CDK4</i> (OR 2.36 [1.27–4.37], <i>p</i> = 0.036) genes, as well as wild type <i>EGFR</i> (OR 0.33 [0.20–0.53], <i>p</i> = 0.008). Cystic GBM was not associated with overall survival (HR 0.82 [0.61–1.11], <i>p</i> = 0.205). Cystic GBM is marked by&#xa0;alterations of the Rb and p53 pathways as well as <i>KDR</i> alterations. This provides new insights into the pathogenesis of cystic GBM. Several alterations associated with cystic GBM, including <i>CDK4</i> and <i>KDR</i>, are targets of small-molecule inhibitors. Further research is required to explore the diagnostic and therapeutic implications of this association.</p>

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Cystic glioblastoma is associated with alterations of KDR and the Rb pathway: a single-center retrospective analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月14日

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  • Johannes Werner,
  • Sahar Alizada,
  • Cheuk Hong Leung,
  • Heather Lin,
  • Ahmed Msherghi,
  • Erick Campbell,
  • Chetna Wathoo,
  • Chibawanye I. Ene,
  • Maria A. Gubbiotti,
  • Vinay Puduvalli,
  • Max Wintermark,
  • Nazanin K. Majd

摘要

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Cystic GBM is a phenotypic subset requiring distinct clinical management. This study aimed to comprehensively assess the genomic landscape of cystic GBM. GBM, IDH wild-type patients with available next-generation sequencing and presurgical brain MRI data were evaluated for cysts by neuroimaging specialists and a senior neuroradiologist. Patients with incomplete radiological or histopathological data, treatment-related cysts, or indeterminate cyst status were excluded. We used logistic regression to assess the association of cystic GBM with demographic variables and the top 24 altered genes. We employed Cox regression to analyze the association of cystic GBM with survival. Among 374 eligible patients, we identified 111 (30%) with cystic GBM and 263 (70%) with non-cystic GBM. Multivariable logistic regression revealed the association of cystic GBM with alterations of the KDR (OR 8.75 [1.77–43.3], p = 0.038), RB1 (OR 5.12 [2.58–10.1], p = 0.008), TP53 (OR 2.72 [1.67–4.43], p = 0.008), CDK4 (OR 2.36 [1.27–4.37], p = 0.036) genes, as well as wild type EGFR (OR 0.33 [0.20–0.53], p = 0.008). Cystic GBM was not associated with overall survival (HR 0.82 [0.61–1.11], p = 0.205). Cystic GBM is marked by alterations of the Rb and p53 pathways as well as KDR alterations. This provides new insights into the pathogenesis of cystic GBM. Several alterations associated with cystic GBM, including CDK4 and KDR, are targets of small-molecule inhibitors. Further research is required to explore the diagnostic and therapeutic implications of this association.