HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma.
Chromosomal rearrangements of the RET proto-oncogene (RET/PTC) are the common feature of papillary thyroid carcinoma (PTC). In this study, we report the identification, cloning, and functional characterization of a novel type of RET/PTC rearrangement that results from the fusion of the 3'-portion of RET coding for the tyrosine kinase (TK) domain of the receptor to the 5'-portion of the Homo sapiens hook homolog 3 (HOOK3) gene. The novel fusion was identified in a case of PTC that revealed a gene expression signature characteristic of RET/PTC on DNA microarray analysis, but was negative for the most common types of RET rearrangement. A fusion product between exon 11 of HOOK3 and exon 12 of RET gene was identified by 5'RACE, and the presence of chimeric HOOK3-RET protein of 88 kDa was detected by western blot analysis with an anti-RET antibody. The protein is predicted to contain a portion of the coiled-coil domains of HOOK3 and the intact TK domain of RET. Expression of the HOOK3-RET cDNA in NIH3T3 cells resulted in the formation of transformed foci and in tumor formation after injection into nude mice, confirming the oncogenic nature of HOOK3-RET.
Ciampi
Raffaele
R
Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Giordano
Thomas J
TJ
Wikenheiser-Brokamp
Kathryn
K
Koenig
Ronald J
RJ
Nikiforov
Yuri E
YE
D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics; D041681:NIH 3T3 Cells; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D011995:Recombination, Genetic; D013964:Thyroid Neoplasms / Q000235:genetics*
C524294:HOOK3-RET fusion protein, human; C000715470:MAS1 protein, human; D008869:Microtubule-Associated Proteins; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; C425466:hook3 protein, human; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human