title: Identification of a novel subtype of H4-RET rearrangement in a thyroid papillary carcinoma and lymph node metastasis.
abstract: RET/PTC chimeric oncogenes are generated by the fusion of heterologous genes to the RET tyrosine kinase encoding domain. These rearrangements are typical of papillary thyroid carcinomas. RET/PTC1 is one of the most frequently found RET/PTC version and, in all the cases so far reported, it is invariably generated by the fusion of the first encoding exon of the H4 gene to the RET kinase encoding domain. This results in the generation of an oncogenic protein containing the first 101 residues of the H4 protein at the N-terminus. We report the isolation of a novel subtype of H4-RET fusion, designated RET/PTC1L, from a human papillary carcinoma of the thyroid and lymph node metastasis. At variance with the classic one, this novel rearrangement generates a protein containing the N-terminal 150 residues of H4. RET/PTC1L is able to transform NIH 3T3 cells; its transforming ability, however, is 5-fold lower than that of the classic RET/PTC1 isoform. We propose that RET/PTC1L is a novel chimeric oncogene involved in thyroid tumorigenesis; its low transforming ability may be one of the reasons explaining the low frequency by which it is found in human thyroid carcinomas.
authors.affiliation: Dipartimento di Oncologia, I-56126 Pisa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Giannini
authors.forename: G
authors.initials: G
authors.lastname: Salvatore
authors.forename: C
authors.initials: C
authors.lastname: Monaco
authors.forename: F
authors.initials: F
authors.lastname: Sferratore
authors.forename: L
authors.initials: L
authors.lastname: Pollina
authors.forename: F
authors.initials: F
authors.lastname: Pacini
authors.forename: F
authors.initials: F
authors.lastname: Basolo
authors.forename: A
authors.initials: A
authors.lastname: Fusco
authors.forename: M
authors.initials: M
authors.lastname: Santoro
mesh_terms: D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D003001:Cloning, Molecular; D015321:Gene Rearrangement; D006801:Humans; D008207:Lymphatic Metastasis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human