Detection of mitochondrial DNA mutations in pancreatic cancer offers a "mass"-ive advantage over detection of nuclear DNA mutations

We sequenced the complete 16.5-kb mitochondrial genome (mtDNA) in 15 pancre atic cancer cell lines and xenografts. Homoplasmic mtDNA somatic mutations and novel variants were identified in nearly all samples. Southern blot ana lysis and direct sequencing of mutation sites showed that the intracellular mass of mtDNA was greatly (6-8-fold) increased in pancreatic cancer cells in relation to corresponding normal cells; this property accounted for and greatly facilitated the identification of these mutations among the dense d esmoplastic host reaction characteristic of primary pancreatic cancers. Str uctural characteristics and mathematical modeling of the evolution of mtDNA mutations suggested that many of the mutations identified might represent a random evolution of homoplasmic variants, rather than necessarily being a product of selective pressures, Complete sequencing of the nuclear MnSOD g ene, which protects cells from the mitogenic and toxic effects of oxygen ra dicals, did not reveal any mutations. Nevertheless, the nearly ubiquitous p revalence and high copy number of mtDNA mutations suggest that they be cons idered of promising clinical utility in diagnostic applications.