Triplication of one chromosome no. 15 with an altered C‐myc containing ecori fragment and elimination of the normal homologue in a T‐cell lymphoma line of akr origin (TIKAUT)

Abstract

An ouabain- and thioguanine-resistant subline (TIKAUT) of spontaneous AKR lymphoma, TKA, was trisomic for chromosome 15 and contained a single 33 kb EcoRI fragment, containing the oncogene c-myc. The original TKA lymphoma and derived in vitro line contained the same 33 kb fragment, as well as a normal 22 kb fragment. It has been concluded that the original 15-trisomic TKA tumor has duplicated a 15-chromosome that contained the changed fragment, while maintaining the normal fragment as well. Subsequently, in the derived TIKAUT line, the changed chromosome duplicated again, giving rise to three copies, and the normal homologue was eliminated altogether. This confirms our earlier somatic hybrid study showing that the duplicated 15-chromosome of a T-cell leukemia confers an advantage on the cell that favors tumorigenicity, whereas the normal homologue exerts a counteracting influence. Therefore, in the course of tumor progression, the changed chromosome tends to be amplified, whereas its normal homologue tends to be eliminated.

Epstein-Barr virus-transformed pro-B cells are prone to illegitimate recombination between the switch region of the mu chain gene and other chromosomes.

“…In sporadic BL, the predominant breakpoint is in S., as in the FLEB translocations. It has been suggested (27) (33,34). The duplication of the 14q+ marker and the loss of its normal homologue supports the hypothesis that the rearranged chromosome conveys a selective growth advantage on the cell in a dose-dependent manner.…”

“…The duplication of the 14q+ marker and the loss of its normal homologue supports the hypothesis that the rearranged chromosome conveys a selective growth advantage on the cell in a dose-dependent manner. The loss of the normal homologue may be coincidental or reflect some trans-acting negative control, as suggested in the murine systems (23,33,34).…”

Further studies on chromosome 15 trisomy in murine T‐cell lymphomas: Mapping of the relevant chromosome segment

“…This can be exemplified by the regular duplication of the APR-derived chromosome 15 in trisomic T-cell leukedepending on the genetic origin of chromosome 15. This was an autonomous property of chromosome 15, rather than of the genetic background (Wiener et al, 1980(Wiener et al, , 1982.…”

“…Translocations that involved other chromosomes than No. 15 did not duplicate (Spira et al, , 1983Wiener et al, 1982). Chromosome 15 trisomic T-cell lymphomas induced in reciprocal (14; 15)-translocation-~arry-ing CBAT6T6 mice have duplicated the segment distal to the T6 breakpoint (band B 1/2), indicating that the relevant gene was in the distal part of the chromosome (Wiener et al, 1978b.…”

“…Chromosomes 15, derived from different mouse strains, differ in their propensity to duplicate during T-cell leukemogenesis in Fl hybrids. The AKR-derived chromosome 15 was found to duplicate preferentially in each F1 combination where the high leukemic AKR strain was one of the parents (Wiener et al, , 1980(Wiener et al, , 1982Wirschubsky et al, 1984~). The chromosomes of different strains could be arranged as a consistent "hierarchical series", based on similar preferential duplications.…”