Translocation in a carcinoma

Chromosomal translocations that encode fusion oncoproteins are common in leukemias/lymphomas and sarcomas, but not in carcinomas, which constitute up to 90% of human cancers. In the August 25 Science, Kroll et al. report the detection of a Pax8-PPARγ1 fusion in five of eight thyroid follicular carcinomas (Science 2000, 289:1357-1360). Pax8 is a transcription factor essential for formation of the thyroid follicular epithelial lineage, whereas the peroxisome proliferator-activated receptor (PPAR) γ1 can inhibit the growth and promote the differentiation of cancer cell lines. Based on in vitro studies, the fusion proteins appear to be acting as dominant negatives, interfering with the normal activity of PPARγ1. The identification of Pax8-PPARγ1 may help in the differentiation of follicular carcinomas (potentially malignant) and follicular adenomas (benign, and lacking in the fusion oncoprotein).