Reciprocal products of chromosomal translocations in human cancer pathogenesis: key players or innocent bystanders?
Chromosomal translocations are frequently involved in the pathogenesis of leukemias, lymphomas and sarcomas. They can lead to aberrant expression of oncogenes or the generation of chimeric proteins. Classically, one of the products is thought to be oncogenic. For example, in acute promyelocytic leukaemia (APL), reciprocal chromosomal translocations involving the retinoic acid receptor alpha (RARalpha) gene lead to the formation of two fusion genes: X-RARalpha and RARalpha-X (where X is the alternative RARalpha fusion partner: PML, PLZF, NPM, NuMA and STAT 5b). The X-RARalpha fusion protein is indeed oncogenic. However, recent data indicate that the RARalpha-X product is also critical in determining the biological features of this leukemia. Here, we review the current knowledge on the role of reciprocal products in cancer pathogenesis, and highlight how their expression might impact on the biology of their respective tumour types.
Rego
Eduardo M
EM
Molecular Biology Program, Dept of Pathology, Memorial Sloan-Kettering Cancer Center, Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.
Pandolfi
Pier Paolo
PP
D000818:Animals; D002877:Chromosomes, Human / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D014178:Translocation, Genetic
D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D020558:GTP Phosphohydrolases