Clonal evolution of N-methylnitrosourea-induced C57BL/6J thymic lymphomas by analysis of multiple genetic alterations.
C57BL/6J mice were treated with N-methylnitrosourea (NMU) and the evolution of leukemic T-cells clones into frank thymic lymphomas was followed in 42 animals using serology of T-cell markers, rearrangements of the T-cell receptor genes gamma, beta1 and beta2 and detection of carcinogen-induced Ki-ras mutations and trisomy of chromosome 15. During the latent period, multiple populations of T-cell clones were present in the thymus, many contained trisomy 15, but few had detectable Ki-ras mutations. Since most frank lymphomas consisted of a single T-cell clone with both a mutation of Ki-ras and trisomy 15, the results imply that these two events are critical for the evolution of T-cell clones from the preleukemic phase to a more malignant disease stage. Progression to frank lymphomas is coincident with changes in the expression pattern of the T-cell growth factor interleukin-2 receptor, which may play a role in the selection, expansion and thymus-independent growth of a T-cell clone.
Newcomb
E W
EW
Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, U.S.A.
D000818:Animals; D002273:Carcinogens; D002999:Clone Cells; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D008223:Lymphoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D008770:Methylnitrosourea; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D013953:Thymus Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D014314:Trisomy
D002273:Carcinogens; D008770:Methylnitrosourea