Kim Hong Sug, Lim Hee Sun, Lee Sug Hyung, Lee Jong Woo, Nam Suk Woo, Park Won Sang, Lee Youn Soo, Lee Jung Young, Yoo Nam Jin
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Int J Cancer. 2006 Dec 1;119(11):2607-11. doi: 10.1002/ijc.22244.
Mitochondrial microsatellite instability (mtMSI) and mutations of mitochondrial DNA has been reported in cancer epithelia of carcinomas. However, mtMSI in cancer stroma has not yet been identified in human cancers. In this study, we attempted to determine if mtMSI occurs in the cancer stroma of sporadic colorectal cancers, and if the stromal mtMSI has any correlations with stromal nuclear MSI (nMSI) and cancer epithelial mtMSI. Nine microsatellite sequences within the D-loop and 5 coding genes for mtMSI, and 9 microsatellites for nMSI were analyzed in the microdissected cancer epithelia and adjacent stromas of 48 sporadic colorectal cancers. Overall, 23 somatic mitochondrial DNA alterations were detected in 15 cancer epithelia (31.2%) and 5 stromas (10.4%). The mutations consisted of 19 D-loop mtMSI alterations, and 1 missense and 3 framshift mutations of repeat sequences within the coding genes. All of the 5 stromal genetic alterations showed D-loop mtMSI. In regards to other MSI status, the stromal mtMSI had no association with stromal nMSI or epithelial mtMSI, either. These findings indicate that in addition to the cancer epithelia the cancer stroma harbor mtMSI, and suggest a possible role of stromal mtMSI in the pathogenesis of colorectal cancers. Furthermore, the data suggest that stromal mtMSI may occur independently of stromal nMSI and epithelial mtMSI in sporadic colorectal cancers.
线粒体微卫星不稳定性（mtMSI）及线粒体DNA突变已在癌上皮组织中被报道。然而，人类癌症中尚未发现癌基质中的mtMSI。在本研究中，我们试图确定散发性结直肠癌的癌基质中是否存在mtMSI，以及基质mtMSI与基质核微卫星不稳定性（nMSI）和癌上皮mtMSI是否存在任何关联。对48例散发性结直肠癌的显微切割癌上皮组织及相邻基质中D环内的9个微卫星序列、5个用于mtMSI的编码基因以及9个用于nMSI的微卫星进行了分析。总体而言，在15个癌上皮组织（31.2%）和5个基质（10.4%）中检测到23个体细胞线粒体DNA改变。这些突变包括19个D环mtMSI改变，以及编码基因内重复序列的1个错义突变和3个移码突变。所有5个基质基因改变均显示为D环mtMSI。关于其他微卫星不稳定性状态，基质mtMSI与基质nMSI或上皮mtMSI也无关联。这些发现表明，除癌上皮组织外，癌基质中也存在mtMSI，并提示基质mtMSI在结直肠癌发病机制中可能发挥作用。此外，数据表明散发性结直肠癌中基质mtMSI可能独立于基质nMSI和上皮mtMSI而发生。
