High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma.
We had previously detected a transforming oncogene, designated PTC, in 25% of 20 papillary thyroid carcinomas. In order to characterize further the transforming activity of this tumour histotype, a new panel of tumour specimens from 16 patients was analysed by using a modified calcium phosphate-DNA coprecipitation transfection protocol. Tumour DNA from 10 patients (62%) displayed a transforming activity due to activation of three different oncogenes identified in four cases as PTC, in four cases as TRK, and in two cases as N-RAS. The same structural alterations of PTC and TRK (gene rearrangements) as well as of N-RAS (point mutation) detected in the NIH3T3 transformants, were also found in the original tumour DNAs, thus indicating that their activation was not due to transfection procedures. Since both PTC, a novel rearranged form of RET, and TRK display a tyrosine protein kinase activity, it is proposed that the activation of this class of oncogenes is specifically involved in the pathogenesis of papillary thyroid cancer.
Bongarzone
I
I
Divisione di Oncologia Sperimentale A, Istituto Nazionale Tumori, Milan, Italy.
Pierotti
M A
MA
Monzini
N
N
Mondellini
P
P
Manenti
G
G
Donghi
R
R
Pilotti
S
S
Grieco
M
M
Santoro
M
M
Fusco
A
A
D000818:Animals; D015139:Blotting, Southern; D002291:Carcinoma, Papillary / Q000201:enzymology / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics*; D014162:Transfection
D004273:DNA, Neoplasm; D011505:Protein-Tyrosine Kinases