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 with papillary thyroid carcinoma (PTC) after their exposure to radioactive iodine after the Chernobyl reactor accident, new methods for the detection of novel types of RET rearrangements are being developed. In this study, an...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2000-12, Vol.60 (24), p.7028-7032
Main Authors: KLUGBAUER, Sabine, JAUCH, Anna, LENGFELDER, Edmund, DEMIDCHIK, Evgenij, RABES, Hartmut M
Format: Article
Language:English
Subjects:
Adolescent
Amino Acid Sequence
Base Sequence
Biological and medical sciences
Blotting, Northern
Carcinoma, Papillary - genetics
Chromosomes, Human, Pair 18
Cytoplasm - metabolism
DNA, Complementary - metabolism
Drosophila Proteins
Endocrinopathies
Female
Gene Rearrangement
Humans
In Situ Hybridization, Fluorescence
Male
Malignant tumors
Medical sciences
Molecular Sequence Data
Power Plants
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
Radioactive Hazard Release
Receptor Protein-Tyrosine Kinases - genetics
RET gene
Reverse Transcriptase Polymerase Chain Reaction
RFG8 gene
RNA, Messenger - metabolism
Thyroid Neoplasms - genetics
Thyroid. Thyroid axis (diseases)
Tissue Distribution
Translocation, Genetic
Ukraine
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Summary:As part of ongoing studies on the RET rearrangement frequency in children with papillary thyroid carcinoma (PTC) after their exposure to radioactive iodine after the Chernobyl reactor accident, new methods for the detection of novel types of RET rearrangements are being developed. In this study, an improved reverse transcription-PCR strategy is used successfully to identify a new type of RET rearrangement. This rearrangement is designated PTC8 and the involved RET-fused gene (RFG) as RFG8. The identification of two reciprocal transcripts coding for the RFG8/RET and RET/RFG8 fusions suggests that the PTC8 rearrangement results from a balanced chromosomal translocation. With a view to clarify its role in tumor induction, we compared the fusion products with those of previously described RET rearrangements. We therefore sequenced and characterized the RFG8 cDNA, which showed no significant similarity to any functional protein described as yet. RFG8 is located on chromosome 18q21-22 and is expressed ubiquitously. Bioinformatic analysis predicts with a high probability that the corresponding rfg8 protein is located in the cytoplasm and is involved putatively in intracellular transport processes. Furthermore, we identified coiled-coil structures upstream of the breakpoint with one of the coiled-coils showing dimerization capability. Thus the rfg8/ret fusion protein exhibits structures for oncogenic activation that are similar to those observed in previously described RET fusions.
ISSN:0008-5472
1538-7445