Mitochondrial DNA copy number changes in human gliomas.

Gene amplification has been found to be biologically important in cancer. We report a complementary DNA sequence obtained using a subtractive hybridization approach which is frequently and highly amplified in human gliomas. 39/45 (87%) glial tumor specimens (of pathologically low and high grade) revealed increases in copy number of this clone from 5- to 25- fold; erb-b amplification was found in 8/45 (18%). This clone revealed homology to non-continuous mitochondrial DNA positions 1679-1948 and 2017-2057, with the interspersed sequences deleted. A non-mitochondrial genomic addition of 15 bases at the 5' end of the clone and a 7 base insertion adjacent to position 1948 were also present. Evaluation of the entire mitochondrial genome in a subset of 11 tumors showed maximal amplification between mitochondrial positions 748 and 5882, and a lower degree of amplification elsewhere, with a recurrent deletion of a 1.2 kb EcoRI fragment noted in 5/11 (46%) tumors. The mitochondrial genome is frequently affected in human gliomas, and warrants further study to determine its role in glial malignancy.