6;7 Chromosomal Translocation in Spontaneously Arising Rat Immunocytomas: Evidence for c-myc Breakpoint Clustering and Correlation Between Isotypic Expression and the c-myc Target

Abstract

Our previous studies have shown that spontaneously arising immunocytomas in the LOU/Ws1 strain of rats contain a t(6;7) chromosomal translocation in all seven tumors studied (F. M. Babonits, J. Spira, G. Klein, and H. Bazin, Int. J. Cancer 29:431-437, 1982). We have also shown that the c-myc is located on chromosome 7 (J. Sümegi, J. Spira, H. Bazin, J. Szpirer, G. Levan, and G. Klein, Nature (London) 306:497-499, 1983) and the immunoglobulin H cluster on chromosome 6 (W.S. Pear, G. Wahlström, J. Szpirer, G. Levan, G. Klein, and J. Sümegi, Immunogenetics 23:393-395, 1986). We now report a detailed cytogenetic and molecular analysis of nine additional rat immunocytomas. The t(6;7) chromosomal translocation is found in all tumors. Mapping of the c-myc breakpoints showed that in 10 of 14 tumors, the c-myc breakpoints are clustered in a 1.5-kilobase region upstream of exon 1. In contrast with sporadic Burkitt's lymphoma and mouse plasmacytoma, only 1 of 14 tumors contains the c-myc breakpoints in either exon 1 or intron 1. Analysis of the sequences juxtaposed to the c-myc show that immunoglobulin H switch regions are the targets in at least five tumors and that there is a strong correlation between the secreted immunoglobulin and the c-myc target. Unlike sporadic Burkitt's lymphoma and mouse plasmacytoma, at least two rat immunocytomas show recombination of the c-myc with sequences distinct from immunoglobulin switch regions.