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.
Department of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano (PN), Italy.
D
D
Gasparotto
R
R
Maestro
T
T
Vukosavljevic
S
S
Piccinin
A
A
Sandrin
S
S
Rizzo
M
M
Boiocchi
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