Amplified extrachromosomal elements containing c-Myc and Pvt 1 in a mouse plasmacytoma

Abstract

After adaptation of a mouse plasma cell tumor, MOPC265, to culture, we have found several unique chromosomal alterations in addition to the T(12;15) translocation and trisomy 11 frequently observed in plasmacytomas. Among these alterations is a specific coamplification of the c-Myc and Pvt 1 gene loci from mouse chromosome 15. Further analysis by fluorescence in situ hybridization demonstrates that the amplicons of c-Myc and Pvt 1 exist as extrachromosomal elements as well as within intact chromosomes. Most importantly, the presence of both Pvt 1 and c-Myc in these extrachromosomal elements indicates ongoing coselection for these loci in the propagation of MOPC265.

Myc/p53 interactions in transgenic mouse mammary development, tumorigenesis and chromosomal instability

“…However, our studies with a chromosome 11-speci®c FISH probe made from the mouse Brca1 gene, which is located at 11D (SchroÈ ck et al, 1996b), using G-banding indicate that the chromosomal breakpoint of the translocation is telomeric to both p53 and Brca1 in at least 2 cases (66a7 and myc83) (data not shown). These data provide further evidence that the telomeric end of mouse chromosome 11, which exhibits a high degree of conservation with human chromosome 17, contains critical genes involved in both growth suppression (Plummer et al, 1997) and cell transformation (Buchberg et al, 1989;Mai et al, 1995).…”

“…These results implicate a region that is involving or telomeric to 11D in the process of c-myc-initiated tumorigenesis, as determined by FISH mapping with Brca1. Furthermore, in previous studies with mouse plasmacytomas, a trisomy of chromosome 11 was frequently observed in addition to the T(12 : 15) translocation which causes deregulation of c-myc expression (Mai et al, 1995). Interestingly, the distal region of murine chromosome 11 exhibits extensive linkage conservation with human chromosome 17 (Buchberg et al, 1989) and in addition to p53 and Brca1, this chromosome may contain other genes involved in the tumorigenic process (Plummer et al, 1997).…”

BRCA1 binds c-Myc and inhibits its transcriptional and transforming activity in cells

“…In this regard, wild type p53 can reduce transcription from the c-Myc promoter in vitro (Ragimov et al, 1993) by interference with assembly of the transcription preinitiation complex. Finally, c-Myc overexpression precedes c-Myc gene ampli®cation (Mai et al, 1995), suggesting that elevated Myc protein levels play a role in amplification of chromosomal events.…”

Genomic instability and apoptosis are frequent in p53 deficient young mice

“…Moreover, the c-myc gene was both translocated and ampli®ed, and the protein was overexpressed in mouse plasmacytoma cells (Mai et al, 1995). In this study, we tested the genomic stability of c-myc, DHFR, and CAD, all of which were ampli®ed concomitant with c-Myc overexpression in cells isolated from p53 7/7 cells (Yin et al, 1992;Livingstone et al, 1992).…”

“…Ten-day-old skin-and spleen-derived primary ®broblasts (passage 0) were also obtained from these mice by explanting subcutaneous skin tissue pieces and spleen fragments into RPMI 1640 medium supple- 7/7 cells exhibit atypical chromsome morphology, gene ampli®cation, elevated c-Myc protein levels and abnormally ampli®ed centrosomes. Metaphase plates were prepared and evaluated as described (Mai, 1994;Mai et al, 1995Mai et al, , 1996. (a) shows a p53 7/7 thymus-derived Giemsa-stained aneuploid metaphase plate.…”