CBMT-24. MITOCHONDRIAL DNA CONTENT IN GLIOBLASTOMA AND ITS CLINICAL SIGNIFICANCE

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 20; no. suppl_6; p. vi37
• Main Authors: Sravya, Palavalasa, Rao, Shilpa, Nimbalkar, Vidya, Kanuri, Nandaki, Banavathy, Kruthika, Arimappamagan, Arivazhagan, Somanna, Sampath, Santosh, Vani
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 05.11.2018
• Subjects: Abstracts
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noy148.143

Abstract Evidence of altered mitochondrial DNA (mtDNA) content in several malignancies has surfaced in recent years. However, in glioblastoma, this aspect remains obscure. Hence, we have studied mtDNA content in glioblastoma at diagnosis and recurrence. METHODS Formalin fixed paraffin embedded tissue of newly diagnosed glioblastoma (n=100), paired recurrent glioblastoma (n=16 pairs) and non-neoplastic brain (n=30) archived in the department of Neuropathology, NIMHANS, were utilized for the study. Clinical details of the patients were obtained from files. IDH, ATRX and TERT promoter mutations, MGMT promoter methylation and EGFR amplification were assessed using immunohistochemistry, Sanger’s sequencing, methylation specific PCR and fluorescent insitu hybridization. mtDNA copy number was analyzed using quantitative real time PCR (relative quantification). The mtDNA content was calculated as percentage of normal using the formula 2- ΔΔCT x 100. Hence, for example, 20% mtDNA copy number means that if non-neoplastic brain tissue contains 100 copies of mtDNA, the tumor contains only 20 copies. RESULTS mtDNA content was lower than non-neoplastic brain tissue (mean mtDNA copy number 19.8%) in all cases. Among them, the mtDNA content was significantly lower in older patients (p=0.04). Tumors expressing markers of aggressiveness had lower mtDNA content, though the difference was not statistically significant. Survival analysis using Cox regression showed that lower mtDNA copy number is associated with higher risk and hence poorer prognosis (Exp(B):0.97; p=0.045). Of the16 patients with recurrence studied, 7 had received radiation therapy (RT) while the others defaulted or recurred before initiation of RT. mtDNA content had increased at recurrence(mean:48.02%) when compared to the primary tumor(mean:20.32%) in all 7 cases who received RT. In the remaining 9 cases who did not receive RT, the difference was not statistically significant. Thus, for the first time, we show that lower mtDNA copy number is associated with poorer survival and earlier recurrence in glioblastoma and that RT may increase the mtDNA content.