Karyotypic progression in human tumors

Abstract

Karyotypic progression may be viewed in at least two ways. One approach seeks evidence for increasing and progressive deviation from the normal chromosome pattern in tumors. The clearest examples, found in some leukemias, are those in which successive karyotypic changes are superimposed on an already aberrant cell population. Evidence of chromosomal progression within solid tumors is far less frequent, possibly because the tumors themselves are at a relatively late stage in their evolution. An alternative approach, therefore, attempts to correlate the extent of karyotypic deviation with other aspects of tumor progression. Recent data, based on classical cytogenetic analyses and flow cytometry, are presented to determine relationships between karyotype and specific origin and morphology of tumors. The predominant theme which emerges, not surprisingly, is that the more deviant chromosome patterns are associated with other measures of increased biologic malignancy. What is surprising is the degree to which these properties are expressed in primary tumors and the relative lack of evidence for further karyotypic evolution with recurrence or metastasis. Examples of genetic instability, evolution through polyploidy, gene amplification, and selection for specific chromosomal rearrangement are found in populations of premalignant and malignant human cells. There is increasing recognition of the importance of tumor-specific chromosome aberrations in the stepwise progression from the normal to the fully neoplastic cell.

Chromosome abnormalities and oncogenesis in cat leukemias

“…They are found in most malignancies that are retrovirus-positive as well as retrovirus-negative (Grindem and Buoen, 1989), with the exception of some tumors caused by retrovirus with one genes; i.e., genes encoding for transformation (Duesberg, 1987 b). Furthermore, chromosomal abnormalities are diagnostic of neoplastic disease (Wolman, 1983). Chromosomal abnormalities are also seen in benign tumors and in non-tumorous cells exhibiting abnormal growth as well (Wurster-Hill et al, 1988).…”

“…These abnormalities may be either random or nonrandom (Maruyama et al, 1990;Haluska et al,1987;Rowley, 1984;Wolman, 1983). Examples of non-random, characteristic abnormalities include translocation t(8;14) or variants thereof, all of which involve a break at band 8q24, in Burkitt's lymphoma (BL); translocation t(15;17) in acute promyelocytic leukemia (APL); translocation t(9;22) or variants, almost always involving chromosome 22 (the Philadelphia chromosome), in chronic myelogenous leukemia (CML) (Rowley, 1990).…”

“…Although the translocation breakpoints can vary, they are usually restricted to the specific region of band 8q24 (Rowley, 1990;van Lohuizen et al, 1989;Morishita et al, 1988;Gough, 1985;Rowley, 1984). The chromosomes involved in the translocation are usually tumor-specific as well, though here too some variation can occur (Haluska et al, 1987;Wolman, 1986;Wolman, 1983;Larson et al, 1981). It is important to note that what may be consistent by cytogenetic analysis may be found to be not totally consistent by molecular analysis; i.e., the former only shows gross abnormalities at the band level, whereas molecular analysis can refine the dissection considerably (WursterHill, personal communication).…”

“…Chromosomal abnormalities are found both in tumors infected by retroviruses without one genes as well as in uninfected tumors (Grindem and Buoen, 1989;Duesberg, 1987 b;Duesberg, 1987 c;Rowley, 1984;Trent, 1984;Wolman, 1983;Levan, 1956). Thus, otherwise indistinguishable tumors may be retrovirus-positive or retrovirus-negative.…”

“…Thus, otherwise indistinguishable tumors may be retrovirus-positive or retrovirus-negative. In fact, chromosomal abnormalities are, at present, the only detectable genetic determinants of tumors (Duesberg, 1987 c;Rowley, 1984;Trent, 1984;Wolman, 1983;Levan, 1956). Therefore, it has been proposed that both virus-positive and virusnegative tumors may be initiated by chromosomal abnormalities, and that transformation can be a virus independent event; i.e., it is not the presence of the retrovirus without one gene that causes cancer but perhaps the processes set forth by the chromosomal abnormalities (Duesberg, 1987 c;Gough, 1985).…”