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Science 289 (5483): 1357-1360

Copyright © 2000 by the American Association for the Advancement of Science

PAX8-PPARgamma 1 Fusion Oncogene in Human Thyroid Carcinoma

Todd G. Kroll,1* Pasha Sarraf,2 Lorenza Pecciarini,1 Chang-Jie Chen,1 Elisabetta Mueller,2 Bruce M. Spiegelman,2 Jonathan A. Fletcher123*

Chromosomal translocations that encode fusion oncoproteins have been observed 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 translocation identified in a subset of human thyroid follicular carcinomas, results in fusion of the DNA binding domains of the thyroid transcription factor PAX8 to domains A to F of the peroxisome proliferator-activated receptor (PPAR) gamma 1. PAX8-PPARgamma 1 mRNA and protein were detected in 5 of 8 thyroid follicular carcinomas but not in 20 follicular adenomas, 10 papillary carcinomas, or 10 multinodular hyperplasias. PAX8-PPARgamma 1 inhibited thiazolidinedione-induced transactivation by PPARgamma 1 in a dominant negative manner. The experiments demonstrate an oncogenic role for PPARgamma and suggest that PAX8-PPARgamma 1 may be useful in the diagnosis and treatment of thyroid carcinoma.

1 Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA, and Harvard Medical School, Boston, MA 02115, USA.
2 Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
3 Departments of Pathology and Pediatric Oncology, Children's Hospital, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: tkroll{at}rics.bwh.harvard.edu; jfletcher{at}rics.bwh.harvard.edu


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