While there have been numerous investigations of the karyotypes of many neoplasms in experi- mental and domestic animals (cf. Sasaki, 1982; Kerler and Rabes, 1994), relatively few constant karyotypic changes occurring in specific histogenetic types of neoplasms have been noted. Table 6.9 shows some examples of known chromosomal abnormalities characteristic of certain neo- plasms in the mouse and the rat. One of the earliest and most frequently studied is the trisomy of chromosome 15 in the mouse, which is found in the vast majority of T-cell lymphomas and leu- kemias regardless of the inducing agent (Sasaki, 1982; Spira, 1983). This change occurs both in
The motifs indicated in the putative fusion proteins are those likely to be the important molecule in tumor pathogenesis. In most cases this is an assumption that is not yet confirmed by functional data.
Key: Known and putative DNA binding and/or protein dimerization motifs—PB, paired box; HD, homeodomain; bZIP, basic region leucine zipper; b-HLH, basic helix-loop-helix mo- tif; ZIP, leucine zipper motif; LIM, cysteine-rich motif. Disease nomenclature: BL, Burkitt lymphoma; FL, follicular lymphoma; AL, acute leukemia; CL, chronic leukemia; ALL, acute lymphocytic leukemia (T- or B-cell); CLL, chronic lymphocytic leukemia (T- or B-cell); PLL, prolymphocytic leukemia; CML, chronic myelogenous leukemia; AML, acute my- elogenous leukemia; APL, acute promyelocytic leukemia; AUL, acute undifferentiated leukemia; NHL, non-Hodgkin lymphoma; CMML, chronic myelomonocytic leukemia; DLCL, diffuse large-cell lymphoma; AD, transcriptional activation domain; TM, TM sequence; RARA, retinoic acid receptor-α receptor; IL, interleukin; Ph, Philadelphia chromosome; Unk, unknown. Further details and specific references may be obtained from the primary source of this table.
From Rabbitts, 1994, with permission of the author and publisher.
spontaneous and chemically and physically induced T-cell neoplasms as well as some B-cell tumors in mice (Spira, 1983). In a related neoplasm, the plasmacytoma induced by pristane in the mouse, regularly translocations involving chromosome 15 are noted in virtually all such neoplasms including those infected with the oncogenic Abelson virus, wherein a somewhat different characteristic translocation and a trisomy of chromosome 11 is noted in contrast to those neoplasms induced by pristane alone (Table 6.9). The (12;15) chromosome translocation causes a juxtaposition of the c-myc proto-oncogene to one of the heavy chain immunoglobulin genes in a head-to-head orientation very much like that seen in the Burkitt lymphoma (8;14) translocation (Wirschubsky et al., 1985; Figure 6.7). The high incidence of the trisomy of chro- mosome 7 seen in mouse skin carcinomas had earlier been seen to a large extent in premalignant skin lesions in the mouse induced by a similar protocol (Aldaz et al., 1989). Interestingly, the virtual absence of trisomy 7 in skin carcinomas induced in mice transgenic for the v-Ha-ras oncogene may be related to the fact that the c-Ha-ras proto-oncogene occurs on that chromo- some (French et al., 1994).
Kerler and Rabes (1994) have reviewed much of the literature on the cytogenetics of rat neoplasms. By combining a number of studies they concluded that the majority (about two- thirds) of the studies exhibited abnormalities in chromosome 2, either numerical or structural. The reference in the table is to a specific study (Sugiyama et al., 1978) which showed that about one quarter of erythroblastic leukemias induced by DMBA exhibited a trisomy of this chromo- some. A trisomy of chromosome 4 was noted in almost all of ENU-induced “neurogenic” neo- plasms in the rat (Au et al., 1977). The most commonly affected chromosome in rat neoplasms is chromosome 1 (Kerler and Rabas, 1994). This is also true in hepatic neoplasms, although abnor- malities in chromosomes 2, 3, 4, 6, 7, 10, and 11 exhibit substantial abnormalities. A major por- tion of the alterations in chromosome 1 are noted in the distal portion of the long arm (Kerler and Rabas, 1994).
Thus, consistent chromosomal abnormalities characteristic of specific histogenetic neo- plasms can be noted in lower animals as well as in humans. Despite these consistencies in both animals and the human, we are still faced with the dilemma of the extensive, apparently random nature of the majority of chromosome abnormalities seen in malignant neoplasms, as well as the question of the primacy of the more specific chromosomal abnormalities in the causation of such neoplasms.