Somatic mutation during metastasis of a mouse fibrosarcoma line detected by DNA fingerprint analysis.
Metastatic nodules were examined by DNA fingerprint analysis. The probes used, Pc-1 and Pc-2, detect mutations as shifts in bands of the minisatellite loci which are dispersed among chromosomes. Four clonal lines of a fibrosarcoma from an F1 mouse (C57BL/Ka x C3H/He) were selected for various metastatic potentials upon inoculation into syngeneic mice. These four lines exhibited many extra bands resulting from recombination and/or DNA slippage, indicating accumulation of mutations during the successive passages in mice. One of the four, a 505 cell line which had been passaged extensively in vitro and consisted of a heterogenous population, was inoculated into thirteen syngeneic mice, and gave rise to six lung metastatic nodules in two mice. All the nodules showed band-patterns distinct from one another, although nodules within a given mouse tended to show similar patterns. When a genetically tagged 505-05-01 clone was analyzed, three of nine metastatic nodules obtained also revealed new bands. These results strongly suggest that somatic mutations occur at a high frequency during metastasis, providing direct evidence of genetic instability of the tumor cells.
Takada
T
T
First Department of Biochemistry, Niigata University School of Medicine.
Suzuki
S
S
Sugawara
Y
Y
Kominami
R
R
Arakawa
M
M
Niwa
O
O
Yokoro
K
K
D000818:Animals; D001483:Base Sequence; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry*; D004276:DNA, Satellite / Q000737:chemistry*; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004276:DNA, Satellite; D008748:Methylcholanthrene