Translocation t(10;14)(q11.2:q22.1) fusing the kinetin to the RET gene creates a novel rearranged form (PTC8) of the RET proto-oncogene in radiation-induced childhood papillary thyroid carcinoma.
Evaluation of 20 cases of radiation-induced childhood papillary thyroid carcinoma using fluorescence in situ hybridization demonstrated the presence of clonal translocations affecting the RET locus. Semiquantitative reverse transcription-PCR indicated overexpression of the RET tyrosine kinase (TK) domain in four cases. In two cases, the RET rearrangements PTC6 and PTC7 were identified and assigned to balanced translocations t(7;10)(q32;q11.2) and t(1;10)(p13;q11.2), respectively. In one case with a balanced translocation t(10;14)(q11.2;q22.1), 5' rapid amplification of cDNA ends revealed a novel type of RET oncogenic activation (PTC8), arising from a fusion of the 5' part of the kinectin (KTN1) gene to the TK domain of the RET gene. The presence of coiled-coil domains in the resulting ktn1/ret fusion protein suggests ligand-independent dimerization and thus constitutive activation of the ret TK domain.
Salassidis
K
K
Institute of Radiation Biology, Ludwig Maximilians University, München, Germany.
Bruch
J
J
Zitzelsberger
H
H
Lengfelder
E
E
Kellerer
A M
AM
Bauchinger
M
M
D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000209:etiology* / Q000235:genetics*; D002478:Cells, Cultured; D018244:Chromosomes, Artificial, Yeast; D002879:Chromosomes, Human, Pair 10; D002883:Chromosomes, Human, Pair 14; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D011210:Power Plants; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000378:metabolism; D018788:Radioactive Hazard Release; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000528:radiation effects; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000235:genetics*; D014178:Translocation, Genetic; D014455:Ukraine
D029721:Drosophila Proteins; C088547:KTN1 protein, human; C000715470:MAS1 protein, human; D008565:Membrane Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila