[Significance of chromosomal abnormalities in solid tumors of humans]

Solid tumours in man are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the tumour and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. Some primary abnormalities are so characteristic as to be virtually pathognomonic for particular types of solid tumours, eg, t (11;22)(q24;q12) in Ewing's sarcoma, t (9,22)(q22;q12) in extraskeletal myxoid chondrosarcoma, t (X;18)(p11;q11) in synovial sarcoma, and t (12;16)(q13;p11) in myxoid liposarcoma. To these purely cytogenetic data implicating specific genetic changes in carcinogenesis may now be added a growing evidence of molecular specificity emerging from recombinant DNA-studies. It appears that both currently known classes of directly cancer-relevant genes, the dominant oncogenes and the recessive tumour suppressor genes, are located at precisely those genomic sites that are visibly involved in neoplasia-associated chromosomal rearrangements. The importance of cytogenetic characterization of solid tumors is thus twofold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality identifies the presence of a neoplastic disease, and the specific type of aberration may reveal the true nature of the tumor and thus improve the diagnostic precision.