Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets
| Autor: | Muhammet Nafi Civan, Ahmet Bekar, Mevlut Ozgur Taskapilioglu, Omer Gokay Argadal, Pinar Eser Ocak, Secil Ak Aksoy, Ismail Seckin Kaya, Sahsine Tolunay, Cagla Tekin, Melis Mutlu, Berrin Tunca, Hasan Kocaeli |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male IDH1 Death-associated protein 6 Molecular classification Biomarkers Tumor Humans Medicine Telomerase ATRX Aged Primary Glioblastoma MALAT1 Brain Neoplasms business.industry General Medicine Middle Aged Prognosis TERT C228T Neurology Mutation Mutation (genetic algorithm) Cancer research Female RNA Long Noncoding sense organs Neurology (clinical) Glioblastoma business |
| Zdroj: | Neurological Research. 43:916-925 |
| ISSN: | 1743-1328 0161-6412 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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