Yayın: Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets
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Tarih
2021-06-21
Kurum Yazarları
Mutlu, Melis
Tekin, Çağla
Civan, Muhammet Nafi
Yazarlar
Ak Aksoy, Seçil
Mutlu, Melis
Tunca, Berrin
Kocaeli, Hasan
Taşkapılıoğlu, Mevlüt Özgür
Bekar, Ahmet
Tekin, Çağla
Arğadal, Ömer Gökay
Civan, Muhammet Nafi
Kaya, İsmail Seçkin
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayımcı
Taylor & Francis
Özet
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.
Açıklama
Anahtar kelimeler
Long noncoding RNA, Pediatric glioblastoma, Tumors, Temozolomide, Glioma, Cells, Atrx, Glioblastoma, IDH1, 2, Tert, MALAT1, Prognosis, Neurosciences & neurology