Frequent and Multiple Mutations at Minisatellite Loci in Sporadic Human Colorectal and Gastric Cancers—Possible Mechanistic Differences from Microsatellite Instability in Cancer Cells

• Published in: Cancer science 2002-04, Vol.93 (4), p.382-388
• Main Authors: Inamori, Hideaki, Takagi, Sachiyo, Tajima, Rie, Ochiai, Masako, Ubagai, Tsuneyuki, Sugimura, Takashi, Nagao, Minako, Nakagama, Hitoshi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cell Line, Tumor; Colorectal cancer; Colorectal Neoplasms - genetics; DNA - genetics; DNA fingerprint analysis; DNA Fingerprinting; DNA Mutational Analysis; DNA probes; Female; Gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Markers; Genomic instability; Health risk assessment; Humans; Male; Medical sciences; Microsatellite instability; Microsatellite Repeats - genetics; Middle Aged; Minisatellite instability; Minisatellite mutation; Minisatellite Repeats; Mutation; Sequence Analysis, DNA; Stomach Neoplasms - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.2002.tb01268.x

Minisatellites (MNs), composed of 5 to 100 nucleotide repeat units, range from 0.5 to 30 kb in length, and have been reported to be mutated in various human malignancies. In this study, frequencies of MN mutations in sporadic human colorectal (34 cases) and gastric cancers (24 cases) at various clinicopathological stages were assessed by multilocus DNA fingerprint analysis with three MN probes, Pc‐1, 33.6 and 33.15. MN mutations were observed in both colorectal and gastric cancers, but at a significantly higher frequency in the former (56%) than in the latter (25%). Multiplicities of MN mutations were 1.50±1.81 and 0.46±1.10 in colorectal and gastric cancers, respectively, and the difference was also significant. Neither the presence nor multiplicity of MN mutations in either colorectal or gastric cancer cases had any correlation with the pathological stage, histological grading or the presence of microsatellite instability (MSI). Although the biological relevance of MN mutations still remains to be clarified, a subset of colorectal and gastric cancers could feature a new type of genomic instability, distinct from MSI.