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

Ak Aksoy S., Mutlu M., Tunca B., Kocaeli H., Taskapilioglu M. Ö., Bekar A., ...Daha Fazla

NEUROLOGICAL RESEARCH, cilt.43, sa.11, ss.916-925, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 43 Sayı: 11
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1080/01616412.2021.1948738
  • Dergi Adı: NEUROLOGICAL RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.916-925
  • Anahtar Kelimeler: Glioblastoma, IDH1, 2, TERT, MALAT1, prognosis, LONG NONCODING RNA, PEDIATRIC GLIOBLASTOMA, TUMORS, TEMOZOLOMIDE, GLIOMA, CELLS, ATRX
  • Bursa Uludağ Üniversitesi Adresli: Evet

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.