HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma
| Autor: | Ronald J. Koenig, Raffaele Ciampi, Kathryn A. Wikenheiser-Brokamp, Yuri E. Nikiforov, Thomas J. Giordano |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities endocrine system Cancer Research Oncogene Proteins Fusion endocrine system diseases Endocrinology Diabetes and Metabolism Papillary Nude Gene Expression Mice Nude Proto-Oncogene Mas Thyroid carcinoma Mice Exon Endocrinology Genetic Western blot Complementary DNA medicine Animals Humans Oncogene Fusion Thyroid Neoplasms Fusion neoplasms Gene Oncogene Proteins Recombination Genetic RET/PTC Rearrangement Genetics medicine.diagnostic_test Chemistry Carcinoma Proto-Oncogene Proteins c-ret Molecular biology Recombination Carcinoma Papillary HOOK3 Female Microtubule-Associated Proteins NIH 3T3 Cells Oncology Diabetes and Metabolism Tyrosine kinase |
| Zdroj: | Endocrine-Related Cancer. 14:445-452 |
| ISSN: | 1479-6821 1351-0088 |
| DOI: | 10.1677/erc-07-0039 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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