The original observation of the Ph1 chromosome by Nowell and Hungerford (1960), a seemingly isolated fact when first reported, has given rise to a major increase in our understanding of the ramifications of somatic mutations in the neoplastic cells. The four examples discussed thus far of the detailed analysis of the translocation-derived chromosomes seen in various lymphomas and leukemias are in fact only the beginning of what promises to be an enormous increase in our understanding not only of the ramification of genetic changes in neoplasia, but also in the struc- ture of the human genome and the potential for genetic alterations residing therein. In Table 6.8 is a reasonably complete listing through 1994 of the known fusion genes and the proteins result- ing from specific translocations not only in lymphomas and leukemias, but also in a number of other solid neoplasms. A number of generalizations resulting from these investigations are slowly developing. As one views the functions of the various genes involved, one is struck by the large numbers of transcription factors and DNA-binding proteins involved in the translocations and ultimately in the fusion proteins. In addition, although thus far a minority, genes involved in signal transduction, including protein kinases and receptors make up most of the remaining functions of the known fusion proteins. There is also the question of the de- or dysregulation of the production of the active component of the fusion protein in which the genes are usually acti- vated either by an increase in their transcription or by an enhanced functional efficiency of the fusion protein itself. Translocations involving immunoglobulin genes or T-cell receptor (TCR) genes (Chapter 19) might be considered a special case since these genes are naturally rearranged in their normal cells for the generation of active immunoglobulins or antigen-receptor genes. As noted from the table, fusion genes may involve tumor suppressor genes (EWS/WT1) or proto- oncogenes as in myc/IgH, TPR/MET, and RET/D10S170. In addition, an interesting fusion of the FUS (also termed the TLS, translocated in liposarcoma) gene fused to the chop gene is seen in myxoid liposarcoma. In this instance the FUS gene codes a nuclear RNA-binding protein, while the chop gene codes a growth arrest gene. Fusion of the two seems to eliminate the RNA- binding domain of FUS with subsequent potential inappropriate targeting of the fusion gene product to regulatory elements normally interacting with FUS alone (Crozat et al., 1993). Inter- estingly, approximately 50% of benign lipomas are characterized by cytogenetic rearrangements involving 12q14-15 in a presumably balanced translocation with a variety of other autosomes as well as the X chromosome (Sreekantaiah et al., 1991). One of the partners in the fusion is the gene, HMGI-C, belonging to the high-mobility group (HMG) family of DNA-binding proteins, possibly playing a role in adipogenesis and mesenchyme differentiation (Ashar et al., 1995). For further information on some of the fusion genes listed in Table 6.8, the references cited should be examined more closely.