Mitochondrial microsatellite instability of colorectal cancer stroma

• Published in: International journal of cancer Vol. 119; no. 11; pp. 2607 - 2611
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-12-2006; Wiley-Liss
• Subjects: Biological and medical sciences; cancer stroma; Chromosome Mapping; colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Loss of Heterozygosity; Medical sciences; Microsatellite Instability; mitochondria; mutation; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Stromal Cells - metabolism; Tumors; microsatellite instability; Rectal disease; mitochondria; Colorectal cancer; Stroma; Mitochondrial DNA; Malignant tumor; Carcinogenesis; Colonic disease; Pregnancy; Cancerology; Microsatellite DNA; Digestive diseases; Genetics; Intestinal disease; Instability; Mutation; cancer stroma
• ISSN: 0020-7136; 1097-0215
• 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. © 2006 Wiley‐Liss, Inc.