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Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets

Ak Aksoy, Secil; Mutlu, Melis; Tunca, Berrin; Kocaeli, Hasan; Taskapilioglu, Mevlut Ozgur; Bekar, Ahmet; Tekin, Cagla; Argadal, Omer Gokay; Civan, Muhammet Nafi; Kaya, Ismail Seckin; Ocak, Pinar Eser; Tolunay, Sahsine


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{
  "DOI": "10.1080/01616412.2021.1948738", 
  "abstract": "Objective: This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX, and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups. Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients. Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001). Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.", 
  "author": [
    {
      "family": "Ak Aksoy", 
      "given": " Secil"
    }, 
    {
      "family": "Mutlu", 
      "given": " Melis"
    }, 
    {
      "family": "Tunca", 
      "given": " Berrin"
    }, 
    {
      "family": "Kocaeli", 
      "given": " Hasan"
    }, 
    {
      "family": "Taskapilioglu", 
      "given": " Mevlut Ozgur"
    }, 
    {
      "family": "Bekar", 
      "given": " Ahmet"
    }, 
    {
      "family": "Tekin", 
      "given": " Cagla"
    }, 
    {
      "family": "Argadal", 
      "given": " Omer Gokay"
    }, 
    {
      "family": "Civan", 
      "given": " Muhammet Nafi"
    }, 
    {
      "family": "Kaya", 
      "given": " Ismail Seckin"
    }, 
    {
      "family": "Ocak", 
      "given": " Pinar Eser"
    }, 
    {
      "family": "Tolunay", 
      "given": " Sahsine"
    }
  ], 
  "container_title": "NEUROLOGICAL RESEARCH", 
  "id": "236606", 
  "issue": "11", 
  "issued": {
    "date-parts": [
      [
        2021, 
        1, 
        1
      ]
    ]
  }, 
  "page": "916-925", 
  "title": "Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets", 
  "type": "article-journal", 
  "volume": "43"
}
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