GENETIC CHANGES IN EPITHELIAL SOLID NEOPLASIA

Although chromosomal analysis of solid epithelial neoplasms has lagged behind that of hematopoietic, mesenchymal, and germ cell tumors, grad ual 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 dif ferent histological types. Most tumors were studied at advanced stages ; therefore, essentially no data are available on the cytogenetic char acteristics of the earliest stages of tumorigenesis. In contrast to th e 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 compl ete than the cytogenetic data, although in cases such as colorectal ca rcinoma, 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 los s of heterozygosity assay directly lead to isolation of a number of tu mor suppressor genes. A comparison of the pattern of deletions identif ied by chromosomal and loss of heterozygosity analysis revealed, as ex pected, a concordance. Comparison of the patterns of chromosomal (and the underlying molecular) changes in tumors between major embryologica l cell types demonstrates fundamental differences in genetic mechanism s which lead to tumorigenesis.