Mitochondrial DNA depletion and its correlation with TFAM, TFB1M, TFB2M and POLG in human diffusely infiltrating astrocytomas

Author(s)

Correia, R. L. ^[1] ; Oba-Shinjo, S. M. ^[1] ; Uno, M. ^[1] ; Huang, N. ^[1] ; Marie, S. K. N. ^[1]

Affiliation

^[1] Univ Sao Paulo, Lab Cellular & Mol Biol, Dept Neurol, Sch Med, BR-01246903 Sao Paulo - Brazil

• Document type: Journal article
• Source: MITOCHONDRION; v. 11, n. 1, p. 48-53, JAN 2011.
• Web of Science Citations: 23

Abstract

Mitochondrial DNA (mtDNA) alterations and their clinical and pathological implications have been analyzed in several human malignancies. A marked decrease in mtDNA copy number along with the increase in malignancy was observed in diffusely infiltrating astrocytomas (24 WHO grade II, 18 grade III, and 78 grade IV or GBM) compared to non-neoplastic brain tissues, being mostly depleted in GBM. Although high relative gene expression levels of mtDNA replication regulators (mitochondrial polymerase catalytic subunit (POLG), transcription factors A (TFAM), B1 (TFB1M) and B2 (TFB2M)) were detected, it cannot successfully revert the mtDNA depletion observed in our samples. On the other hand, a strong correlation among the expression levels of mitochondrial transcription factors corroborates with the TFAM role in the direct control of TFB1M and TFB2M during initiation of mtDNA replication. POLG expression was related to decreased mtDNA copy number, and its overexpression associated with TFAM expression levels also have an impact on long-term survival among GBM patients, interpreted as a potential predictive factor for better prognosis. (C) 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved. (AU)

• FAPESP's process: 04/12133-6 - Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system
• Grantee: Suely Kazue Nagahashi Marie
• Support Opportunities: Research Projects - Thematic Grants