PAX8-PPAR gamma 1 fusion in oncogene human thyroid carcinoma

Chromosomal translocations that encode fusion oncoproteins have been observ ed consistently in leukemias/lymphomas and sarcomas but not in carcinomas, the most common human cancers. Here, we report that t(2;3)(q13;p25), a tran slocation identified in a subset of human thyroid follicular carcinomas, re sults in fusion of the DNA binding domains of the thyroid transcription fac tor PAX8 to domains A to F of the peroxisome proliferator-activated recepto r (PPAR) gamma 1. PAX8-PPAR gamma 1 mRNA and protein were detected in 5 of 8 thyroid follicular carcinomas but not in 20 follicular adenomas, 10 papil lary carcinomas, or 10 multinodular hyperplasias. PAX8-PPAR gamma 1 inhibit ed thiazolidinedione-induced transactivation by PPAR gamma 1 in a dominant negative manner. The experiments demonstrate an oncogenic role for PPAR gam ma and suggest that PAX8-PPAR gamma 1 may be useful in the diagnosis and tr eatment of thyroid carcinoma.