Somatic mitochondrial mutations in pilocytic astrocytoma

The most common brain tumors in childhood and adolescence are low grade pilocytic astrocytomas (PA). Given that an increasing number of mitochondrial defects have been related to brain tumors and cancer in general, we asked whether PAs harbor mutations of mitochondrial DNA (mtDNA). Sequencing analysis of the complete mitochondrial genome of tumor tissue and corresponding blood samples from 19 patients with PA was performed. Of the 19 PA tissue samples, 16 (84%) showed somatic mtDNA mutations, and a total of 34 different somatic mtDNA mutations were identified. Of the 34 mtDNA mutations, 17 (50%) were found in genomic regions involved in pathways of oxidative phosphorylation. Three of the missense mutations in protein coding regions involved change of one amino acid: M60 V in ATP synthase subunit 6, L236I in cytochrome b, and L112 M in cytochrome c oxidase subunit 1. We were able to demonstrate that mtDNA mutations occur in PA and that they are frequently located in protein coding regions. The PA tumors were found to have the highest percentage of mitochondrial mutations of any of the neuroectodermal tumor entities studied to date. To reveal the prognostic importance of these mutations in the tumor biology of PA, larger series need to be studied prospectively.