Bg. Heerdt et al., POLYMORPHISMS, BUT LACK OF MUTATIONS OR INSTABILITY, IN THE PROMOTOR REGION OF THE MITOCHONDRIAL GENOME IN HUMAN COLONIC TUMORS, Cancer research, 54(14), 1994, pp. 3912-3915
The region of the human mitochondrial D-loop has been sequenced from D
NA of colonic tumors and paired normal colonic tissue to determine if
mutations in the promoters for the heavy or light strands are responsi
ble for the decrease in mitochondrial gene expression present in colon
ic tumors. No mutations were detected in the colonic tumors, but new p
olymorphisms, including a sequence analogous to CA microsatellites in
genomic DNA, were revealed. These polymorphisms are restricted to posi
tions within the D-loop which are not essential for accurate and effic
ient in vitro mitochondrial transcription. Thus, these data confirm th
e boundaries of the functional heavy and light strand promoters determ
ined by in vitro assays. Further, although some of the tumors investig
ated show genomic microsatellite instability similar to that recently
reported for colonic tumors, the CA polymorphic region in the mitochon
drial D-loop does not show coincident instability in the tumors. There
fore, as in yeast, there may be both a mitochondrial and a nuclear enz
yme 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 t
he human mitochondrial genome encompassing the heavy and light strand
promoters which can account for the decreased expression of the mitoch
ondrial genome in colonic tumors.