Mitochondrial gene mutation, but not large-scale deletion, is a feature ofcolorectal carcinomas with mitochondrial microsatellite instability

We have shown that microsatellite instability (MSI) occurs in mitochondrial DNA (mtDNA) of colorectal carcinomas. To determine whether such mitochondr ial microsatellite instability (mtMSI) is associated with certain forms of mitochondrial gene alterations, we extended the screening in the same serie s of 45 carcinomas. Analysis by whole mtDNA amplification (16.5 kb) and dig estion revealed no detectable large-scale change in these carcinomas. In co ntrast, single-strand conformation polymorphism (SSCP) analysis demonstrate d NADH dehydrogense (ND) gene alterations in 7 carcinomas (16%), including 3 mononucleotide repeat alterations, 2 missense mutations and 1 small(15 bp ) deletion. Six of these 7 carcinomas also exhibited mtMSI of the (C)n sequ ence in the displacement-loop (D-loop) region. Thus, frameshift or missense mutations rather than large-scale changes in the mtDNA were more common fe atures in colorectal carcinomas with mtMSI. By analogy to mutational featur es of nuclear MSI, mtMSI most likely results from certain repair deficienci es in the mtDNA and probably plays a role in the tumor development of certa in colorectal carcinomas. (C) 1999 Wiley-Liss, Inc.