A t(10;17) translocation creates the RET/PTC2 chimeric transforming sequence in papillary thyroid carcinoma.
Activation of the RET protooncogene tyrosine kinase (tk) by fusion with other genes is a frequent finding in papillary thyroid carcinoma. The tk domain of proto-RET can be fused either with the D10S170 gene generating the RET/PTC1 transforming sequence or with sequences belonging to the gene encoding the regulatory subunit RIA of c-AMP-dependent protein kinase A, thus forming the RET/PTC2 oncogene. We have previously shown that an inversion of chromosome 10, inv(10)(q11.2q21), is responsible for the generation of the RET/PTC1. Here we report that a chromosomal translocation, t(10;17)(q11.2;q23), juxta-poses the tk domain of the RET protooncogene, which resides on chromosome 10, to a 5' portion of the RIA gene on chromosome 17, leading to the formation of the chimeric transforming gene RET/PTC2. The finding of the transforming protein in primary tumor cell extracts supports the conclusion that RET/PTC2 activation plays a role in papillary thyroid tumorigenesis.
Sozzi
G
G
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
Bongarzone
I
I
Miozzo
M
M
Borrello
M G
MG
Blutti
M G
MG
Pilotti
S
S
Della Porta
G
G
Pierotti
M A
MA
D016475:3T3 Cells; D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000648:ultrastructure*; D002886:Chromosomes, Human, Pair 17 / Q000648:ultrastructure*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007621:Karyotyping; D051379:Mice; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D029721:Drosophila Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases