Spontaneous mutation of cell oncogenes plays a minor role in neoplastic transformation of virus-induced murine T-cell lymphomas.
Mink cell focus-forming viruses (MCF) are slow-transforming retroviruses that are able to accelerate the appearance of T-cell lymphomas when injected in newborn AKR mice. Activation of proto-oncogenes by proviral insertion is thought to be the major mechanism by which these viruses exert their oncogenic potential. However, molecular phenomena not strictly virus-determined, such as mutations in cellular oncogenes/tumor suppressor genes or chromosome aberrations, have been hypothesized to contribute to the achievement of the fully neoplastic phenotype in MCF-infected mice. To evaluate the role of spontaneous mutagenesis phenomena in murine virus-induced lymphomagenesis, we analyzed a series of 18 MCF247-induced thymic lymphomas and derived cell lines for the presence of p53 and c-ras gene mutations. Only 1 mutation at the p53 gene and 1 mutation at the ki-ras gene were detected in our study. Our results suggest that spontaneous mutagenesis plays a minor role in virus-induced lymphomagenesis and support the notion that multiple proviral insertions could be the prevalent mechanism of transformation in this experimental system.
Gasparotto
D
D
Department of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano (PN), Italy.
Maestro
R
R
Vukosavljevic
T
T
Piccinin
S
S
Sandrin
A
A
Rizzo
S
S
Boiocchi
M
M
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D011905:Genes, ras / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000821:virology; D051379:Mice; D008806:Mice, Inbred AKR; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D013953:Thymus Neoplasms / Q000235:genetics* / Q000821:virology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53