Molecular analysis of new subtypes of ELE/RET rearrangements, their reciprocal transcripts and breakpoints in papillary thyroid carcinomas of children after Chernobyl.
A high prevalence of RET rearrangements is found in papillary thyroid carcinomas (PTC) of children from Belarus after the Chernobyl reactor accident. The ELE/RET rearrangement (PTC3) is prevailing. Aberrant types of ELE/RET rearrangement have been found with a truncated ELE1 gene: As compared with the common form (PTC3r1) one aberrant type is shorter by one 144 bp exon (PTC3r2) (three cases); in the second atypic form (PTC3r3) the ELE1 part is 18 bp shorter than in PTC3r1. In agreement with the observation that the oncogenic RET is generated by a paracentric inversion at chromosome 10, we found not only ELE/RET, but also RET/ELE transcripts in these tumors. Sequencing of the breakpoint regions at the genomic DNA level revealed DNA modifications that might be relevant for illegitimate recombination after DNA doublestrand breaks. The high prevalence of ELE/RET rearrangements and various subtypes appears to be typical for radiation-induced thyroid carcinomas of children after the Chernobyl reactor accident.
Klugbauer
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S
Institute of Pathology, Ludwig Maximilians University of Munich, Germany.
Demidchik
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EP
Lengfelder
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Rabes
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HM
D019677:Artificial Gene Fusion / Q000528:radiation effects; D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000209:etiology* / Q000235:genetics*; D002675:Child, Preschool; D019457:Chromosome Breakage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000528:radiation effects; D029721:Drosophila Proteins; D005260:Female; D015321:Gene Rearrangement / Q000528:radiation effects*; D016678:Genome; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018788:Radioactive Hazard Release; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000235:genetics*; D014455:Ukraine
D004273:DNA, Neoplasm; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila