Proliferation‐specific and differentiation‐associated chromosomal breakpoints in human neoplasia‐a unifying model

摘要

Based on the consistent pattern of interchromosomal cytogenetic rearrangements in human malignancies, we formulate the hypothesis that one of the breakpoints in a cancer-associated reciprocal translocation is more important to the proliferative, neoplastic process per se, the other, to differentiation-related aspects of the cell type in question. We have attempted to test the intrinsic consistency of this model by interconnecting breakpoints which are known to participate in cancer-associated translocations. The six breakpoint regions informative in this respect were all compatible with the proposed model. An additional 18 breakpoints could be linked to the first six. Of the 12 breakpoint regions classified as proliferation-associated by this approach, eight turned out to be located in bands which also contain cellular oncogenes. On the other hand, only one of the 12 differentiation-associated regions coincided with a known oncogene, location. Thus, there seemed to be a marked correspondence between proliferation-related segments as predicted by the model. and c-one genes. The same model, although originally based on consistent interchromosomal rearrangements, has also been expanded in an attempt to cover even the majority of intrachromosomal aberrations in human neoplasms.