Frequent and multiple mutations at minisatellite loci in sporadic human colorectal and gastric cancers--possible mechanistic differences from microsatellite instability in cancer cells.
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.
Inamori
Hideaki
H
Biochemistry Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Takagi
Sachiyo
S
Tajima
Rie
R
Ochiai
Masako
M
Ubagai
Tsuneyuki
T
Sugimura
Takashi
T
Nagao
Minako
M
Nakagama
Hitoshi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D004247:DNA / Q000235:genetics; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D018598:Minisatellite Repeats; D009154:Mutation; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics*
D005819:Genetic Markers; D004247:DNA