Heerdt B G, Chen J, Stewart L R, Augenlicht L H
Department of Oncology, Albert Einstein Cancer Center, Bronx, New York 10467.
Cancer Res. 1994 Jul 15;54(14):3912-5.
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.
已对结肠癌及配对的正常结肠组织的DNA进行了人线粒体D环区域测序，以确定重链或轻链启动子中的突变是否导致结肠癌中线粒体基因表达降低。在结肠肿瘤中未检测到突变，但发现了新的多态性，包括与基因组DNA中的CA微卫星类似的序列。这些多态性仅限于D环内对体外线粒体转录的准确性和效率并非必需的位置。因此，这些数据证实了通过体外试验确定的功能性重链和轻链启动子的边界。此外，尽管一些研究的肿瘤显示出与最近报道的结肠癌相似的基因组微卫星不稳定性，但线粒体D环中的CA多态性区域在肿瘤中并未显示出一致的不稳定性。因此，与酵母一样，可能存在线粒体和核酶负责错配修复，只有后者参与了某些人类结肠癌中不稳定性的产生。总之，我们的数据未发现人线粒体基因组D环区域中包含重链和轻链启动子的任何结构改变可解释结肠肿瘤中线粒体基因组表达的降低。
