Characterization of an inversion on the long arm of chromosome 10 juxtaposing D10S170 and RET and creating the oncogenic sequence RET/PTC.
RET/PTC is a transforming sequence created by the fusion of the tyrosine kinase domain of the RET protooncogene with the 5' end of the locus D10S170 designated by probe H4 and is frequently found activated in human papillary thyroid carcinomas. RET and D10S170 have been mapped to contiguous regions of the long arm of chromosome 10: q11.2 and q21, respectively. To identify the mechanism leading to the generation of the oncogenic sequence RET/PTC, a combined cytogenetic and molecular analysis of several cases of papillary thyroid carcinomas was done. In four cases the results indicated that these tumors had RET/PTC activation and a paracentric inversion of the long arm of chromosome 10, inv(10)(q11.2q21), with breakpoints coincident with the regions where RET and D10S170 are located. Therefore, a chromosome 10q inversion provides the structural basis for the D10S170-RET fusion that forms the hybrid transforming sequence RET/PTC.
Pierotti
M A
MA
Divisione di Oncologia Sperimentale A, Istituto Nazionale Tumori, Milan, Italy.
Santoro
M
M
Jenkins
R B
RB
Sozzi
G
G
Bongarzone
I
I
Grieco
M
M
Monzini
N
N
Miozzo
M
M
Herrmann
M A
MA
Fusco
A
A
D015139:Blotting, Southern; D002277:Carcinoma / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D007446:Chromosome Inversion; D002879:Chromosomes, Human, Pair 10; D015342:DNA Probes; D029721:Drosophila Proteins; D006801:Humans; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D015183:Restriction Mapping; D013964:Thyroid Neoplasms / Q000235:genetics*
D015342:DNA Probes; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila