A novel type of RET rearrangement (PTC8) in childhood papillary thyroid carcinomas and characterization of the involved gene (RFG8)

As part of ongoing studies on the RET rearrangement frequency in children w ith papillary thyroid carcinoma (PTC) after their exposure to radioactive i odine after the Chernobyl reactor accident, new methods for the detection o f novel types of RET rearrangements are being developed. in this study, an improved reverse transcription-PCR strategy is used successfully to identif y a new type of RET rearrangement. This rearrangement is designated PTC8 an d the involved RET-fused gene (RFG) as RFG8. The identification of two reci procal transcripts coding for the RFG8/RET and RET/RFG8 fusions suggests th at the PTC8 rearrangement results from a balanced chromosomal translocation . With a view to clarify its role in tumor induction, we compared the fusio n products with those of previously described RET rearrangements. We theref ore sequenced and characterized the RFG8 cDNA, which showed no significant similarity to any functional protein described as yet. RFG8 is located on c hromosome 18q21-22 and is expressed ubiquitously. Bioinformatic analysis pr edicts with a high probability that the corresponding rfg8 protein is locat ed in the cytoplasm and is involved putatively in intracellular transport p rocesses. Furthermore, we identified coiled-coil structures upstream of the breakpoint with-one of the coiled-coils showing dimerization capability. T hus the rfg8/ret fusion protein exhibits structures for oncogenic activatio n that are similar to those observed in previously described RET fusions.