ABSTRACT
S pecific chromosomal translocations are found in several solid tumors, including many sarcomas (Table 12.1) and some epithelial tumors (Table 12.2). Several lines o f evidence suggest that the fusion genes en coded by these translocations are the initi ating events that are likely to be necessary for the genesis o f these solid tumors. The resulting fusion proteins are o f two types, most being chimeric transcription factors (or cofactors) and a few representing chimeric tyrosine kinases ( TEL-NTRK3, RET and NTRK1 fusions). Besides their biological interest, these translocations provide diagnostic tumor markers which are especially useful, considering how difficult the morphological diagnosis o f sarcomas can be, even for seasoned sarcoma pathologists. This chapter will highlight molecular diagnostic issues in the detection of gene fusions in solid tumors and will focus on two main methods, namely reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting, using mainly EWS gene fusions as examples. Other diagnostic approaches, such as conventional cytogenetics and fluorescent in situ hybridization are discussed elsewhere in this volume.
