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HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma

2007; Bioscientifica; Volume: 14; Issue: 2 Linguagem: Inglês

10.1677/erc-07-0039

1479-6821

Raffaele Ciampi, Thomas J. Giordano, Kathryn A. Wikenheiser‐Brokamp, Ronald J. Koenig, Yuri E. Nikiforov,

Cancer-related Molecular Pathways

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 .