Polymorphisms, but Lack of Mutations or Instability, in the Promotor Region of the Mitochondrial Genome in Human Colonic Tumors

The region of the human mitochondrial D-loop has been sequenced from DNA of colonic tumors and paired normal colonic tissue to determine if mutations in the promotors for the heavy or light strands are responsible for the decrease in mitochondrial gene expression present in colonic tumors. No mutations were detected in the colonic tumors, but new polymorphisms, including a sequence analogous to CA microsatellites in genomic DNA, were revealed. These polymorphisms are restricted to positions within the D-loop which are not essential for accurate and efficient in vitro mitochondrial transcription. Thus, these data confirm the boundaries of the functional heavy and light strand promotors determined by in vitro assays. Further, although some of the tumors investigated show genomic microsatellite instability similar to that recently reported for colonic tumors, the CA polymorphic region in the mitochondrial D-loop does not show coincident instability in the tumors. Therefore, as in yeast, there may be both a mitochondrial and a nuclear enzyme responsible for mismatch repair, with only the latter involved in generation of instability in some human colon cancers. In summary, our data do not find any structural alterations in the D-loop region of the human mitochondrial genome encompassing the heavy and light strand promotors which can account for the decreased expression of the mitochondrial genome in colonic tumors.