Purpose/results/discussion. Recurrent
chromosomal translocations are common features of many human
malignancies. While such translocations often serve as diagnostic markers, molecular analysis of these breakpoint regions and the characterization of the affected genes is leading to a greater understanding of the causal role such translocations play in malignant transformation. A common theme that is emerging from the study of
tumor-associated translocations is the generation of chimeric genes that, when expressed, frequently retain many of the functional properties of the wild-type genes from which they originated.
Sarcomas, in particular, harbor chimeric genes that are often derived from
transcription factors, suggesting that the resulting chimeric
transcription factors contribute to
tumorigenesis. The
tumor-specific expression of the fusion
proteins make them likely candidates for
tumor-associated
antigens (TAA) and are thus of interest in the development of new
therapies. The focus of this review will be on the translocation events associated with Ewing's
sarcomas/
PNETs (ES),
alveolar rhabdomyosarcoma (ARMS),
malignant melanoma of soft parts (MMSP) (
clear cell sarcoma),
desmoplastic small round cell tumor (DSRCT),
synovial sarcoma (SS), and
liposarcoma (LS), and the potential for targeting the resulting chimeric
proteins in novel
immunotherapies.