PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected].
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) gamma1. PAX8-PPARgamma1 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-PPARgamma1 inhibited thiazolidinedione-induced transactivation by PPARgamma1 in a dominant negative manner. The experiments demonstrate an oncogenic role for PPARgamma and suggest that PAX8-PPARgamma1 may be useful in the diagnosis and treatment of thyroid carcinoma.
Kroll
T G
TG
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. tkroll@rics.bwh.harvard.edu
Sarraf
P
P
Pecciarini
L
L
Chen
C J
CJ
Mueller
E
E
Spiegelman
B M
BM
Fletcher
J A
JA
D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000378:metabolism; D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020218:Response Elements; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; C089946:2,4-thiazolidinedione