Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas

Abstract

Comparative nucleotide sequence analysis of a rearranged c-myc gene in a murine plasmacytoma and c-myc cDNA from normal spleen reveals that chromosomal translocation in the plasmacytoma breaks the c-myc gene within the first exon or intron. In the plasmacytoma truncated c-myc RNAs initiate from newly exposed promoter sites. Nevertheless, the myc polypeptide produced in the plasmacytoma is probably the same as that from the intact c-myc gene because the exon lost by breakage and translocation is non-coding. The second and third exons of the mouse c-myc gene are substantially conserved in the v-myc gene of the avian retrovirus, MC29.

Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus

“…The unrearranged c-myc gene is still present in Manca cells, but our preliminary results from use of Northern probes (probe 2 in Figure 1), S 1 mapping and cDNA cloning indicate that this allele is barely, if at all, expressed. Such a situation has already been reported for a mouse plasmacytoma and may be true for other Burkitt's lymphomas 11,32,34 . Hence, transcriptional activation of the c myc gene appears to be an important result of translocation and in the case described here, it is possible that such activation is largely contributed to by the immunoglobulin heavychain locus enhancer.…”

“…Consistent with this, the transformation frequency of J558L cells by pSV2Δ4 is 5-10-fold lower than the frequency of transformation by pSV2.26 (data not shown). The difference in copy number may also result from a deleterious effect of excess c-myc gene product on J558 cells, which already contain an actively transcribed translocated mouse c-myc gene 32 . If such an effect exists, and if the immunoglobulin heavychain locus enhancer does activate Manca cell c-myc transcription, then there may be a selective advantage to cells transformed with pSV2.26 that retain only one or even no intact copies of the Manca cell c-myc gene.…”

“…As a further result of this deletion the 3.1 kb BglII fragment detected with probe 3 (indicated in b) is only detected in pSV2.26 transformants. Bands labelled J in a are due to the cross-reactivity of probe 1 with normal and rear ranged mouse c-myc genes in J558L cells 11,32 . Restriction sites marked in the lower diagram: R, EcoRI; X, XbaI; H, HindIII; B, BglII; A, AvaI; C, ClaI.…”

“…In these instances, the translocated gene is still transcribed 7,10,11,37 , whilst again the untranslocated gene may be silent 11,32,34 . In these cases, transcription of the translocated c-myc gene may be maintained by a cellular enhancer-type element yet to be identified,…”

Chromosomal translocations deregulating c-myc are associated with normal immune responses

“…These sequences are available from EMBL/GenBank/DDBJ under accession numbers U67968 ± U67983. Translocations denoted BPI and DPI are from Peyer's patches of immunized BALB/c and DBA/2 mice, and BPS and DPS from control BALB/c and DBA/2 mice, respectively , 1977;Husband and Gowans, 1978;Stanton et al, 1983;Strober et al, 1991). Second, the frequency of translocations signi®cantly increases upon gut immunization with cholera toxin, an antigen which induces a predominant IgA response (Table 1) (Lycke and Holmgren, 1986;Lycke and Strober, 1989).…”