Detection of mitochondrial DNA mutations in head and neck cancers

Proc Amer Assoc Cancer Res, Volume 47, 2006 4474 The potential role of mitochondrial DNA (mtDNA) mutations in head and neck tumor development is not well defined. In the present study, we investigated the frequency and distribution of mitochondrial DNA mutations in head and neck tumors and examined relationship between mtDNA mutations and p53 status. Among the 83 samples sequenced, 52 (62.6%) were found to contain somatic mtDNA mutations. MtDNA mutations were identified in both non-coding (D-loop) and coding regions. Further analysis revealed that the mtDNA mutation frequency was different among individual mitochondrial genes. Most mutations were found in D-loop region, and 30 out of the 52 tumors with mutations carried D-loop mutations. All 13 coding genes were found to contain the mtDNA mutations, however, most mutations were detected in ND2 gene (20 out of 52 tumors), a mitochondrial complex I subunit, followed by ND4, and ND5. Since the mitochondrial complex I is a major source of reactive oxygen species, mutations in these subunits of the complex I may significantly change the status of mitochondrial reactive oxygen species, thus contribute to the tumor development. In addition, 16 tumors were found to carry mutations in ATP6. examination of p53 status showed that mtDNA mutations correlated positively with p53 mutations (p < 0.05). Given that the p53 mutations are frequently present in head and neck cancers, dissection of the causal relationship between p53 and mtDNA mutations may unravel new insights into the mechanism of human cancer development. Taken together, these results clearly demonstrate that mtDNA mutations selectively accumulate in certain mitochondrial genes, which may play an important role in the formation and development of head and neck cancers.