NONRANDOM CHROMOSOMAL CHANGE (TRISOMY-11) IN MURINE PLASMACYTOMAS INDUCED BY AN ABL-MYC RETROVIRUS

Trisomy of chromosome 11 (Ts11) is the second most frequent nonrandom chromosomal change in murine plasmacytomas (PCTs). The frequency of Ts 11 is significantly higher in PCTs induced in pristane-conditioned mic e infected by Abelson-murine leukemia virus (52%) compared to those in duced by pristane alone (8.1%). Although the significance of Ts11 in m ouse plasmacytomagenesis is not clearly understood it is hypothesized that a gene or genes located on chromosome (Chr) 11 may specifically p romote the development of PCTs in which both oncogenes, c-myc and v-ab l, are abundantly expressed. To test this assumption we induced PCTs b y three highly effective plasmacytomagenic retroviruses: ABL-MYC, J3V1 , and RIM. Nearly 90% of PCTs that arose in BALB/c, (BALB/c x DBA/2N)F -1, BALB/c-nu/nu, and 5-month-old SCID mice infected with ABL-MYC viru s were trisomic for Chr 11. In contrast, <10% of PCTs induced by J3V1 or RIM retroviral constructs encompassing either v-myc and v-raf or c- myc and v-Ha-ras oncogenes, respectively, contained Ts11. We have also investigated whether the entire Chr 11 or any particular subregion is preferentially duplicated in the process of ABL-MYC plasmacytomagenes is. By inducing PCTs in F1 heterozygous mice that are carriers of reci procal translocations involving Chr 11 we found that the duplicated ch romosomal region is located distal to the T4Dn breakpoint (11B5 band) on the telomeric segment of Chr 11. The regular duplication of this ch romosomal segment strongly suggests the presence of a gene or genes wh ose amplification is of critical importance for v-abl associated murin e plasmacytomagenesis.