Non-random duplication of chromosome 15 in T-cell leukemias induced in mice heterozygous for reciprocal and robertsonian translocations

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Abstract
Two translocation – carrying stocks of mice, T(7;15)9H and Rb(4;15) were resistant to chemical leukemogenesis by 7,12‐dimethylbenz(a)‐anthracene (DMBA) or methyl‐nitroso‐ N‐urea (MNU). Lymphomas were induced in F1 hybrids derived from crossing these two stocks with various susceptible strains. In T‐cell leukemias originating from F1 hybrids with Rb(4;15) as one parent and strain CBA or ASW as the other, the translocation chromosome was present in two copies. In trisomic tumors derived from Rb(4;15) X AKR F1 cross, the AKR‐derived chromosome 15 was duplicated regularly. In contrast, all trisomic lymphomas of the T(7;15)9H F1 outcrosses showed duplication of the non‐translocated chromosome 15 and not of the (7;15) translocation chromosome. It is suggested that the resistance of the T(7;15)9H stock to chemical induction of T‐cell leukemia may be related to the position of the translocation on chromosome 15 (band D2). Our previous studies (reviewed by Klein, 1981) have indicated that this area may contain an oncogene that needs to be activated and subsequently undergo duplication in the course of leukemia development. In our previous studies on trisomic leukemias induced in heterozygotes (Wiener et al., 1979, 1980b), we have found that duplication was nonrandom in all investigated crosses, unless the normal and the translocation marker carrying chromosomes were derived from the same inbred strain. A “duplication preference” scale could be established between chromosomes No. 15 derived from different strains. This suggested that the likelihood of leukemia development was different, depending on the genetic origin of chromosome 15. In the present study, we have found that the duplication of chromosome 15 occurred at random in the CBAT6T6 × C3H F1 cross. This is attributed to the close genetic relationship between the two strains, as indicated by their shared isoenzyme and other markers.