Genetic changes in epithelial solid neoplasia.

Abstract

Although chromosomal analysis of solid epithelial neoplasms has lagged behind that of hematopoietic, mesenchymal, and germ cell tumors, gradual accumulation of data over the past 5 years enables development of a general view. Thus, these tumors appear to be characterized by a set of nonrandom deletions the incidence of which varies in tumors of different histological types. Most tumors were studied at advanced stages; therefore, essentially no data are available on the cytogenetic characteristics of the earliest stages of tumorigenesis. In contrast to the status of cytogenetic data, a large body of information on deletions at the molecular level assayed by the loss of heterozygosity analysis has accumulated over the same period. These data have been less complete than the cytogenetic data, although in cases such as colorectal carcinoma, genetic changes from the earliest to the most advanced stages have been studied in detail providing a genetic view of progression. Equally important is the fact that deletion mapping studies by the loss of heterozygosity assay directly lead to isolation of a number of tumor suppressor genes. A comparison of the pattern of deletions identified by chromosomal and loss of heterozygosity analysis revealed, as expected, a concordance. Comparison of the patterns of chromosomal (and the underlying molecular) changes in tumors between major embryological cell types demonstrates fundamental differences in genetic mechanisms which lead to tumorigenesis.