Comparison of the breakpoint regions of ELE1 and RET genes involved in the generation of RET/PTC3 oncogene in sporadic and in radiation-associated papillary thyroid carcinomas.
The RET/PTC3 oncogene is an activated form of the RET protooncogene, which is frequently rearranged in papillary thyroid carcinoma. RET/PTC3 results from a structural rearrangement between the ELE1 and the RET genes, and it has been observed in both sporadic and radiation-associated post-Chernobyl tumors. To understand the molecular basis that predisposes RET and ELE1 genes to be recurrent targets of "illegitimate" recombination, we examined the genomic regions containing the ELE1/RET breakpoints of six sporadic and three post-Chernobyl tumors in two papillary carcinomas of different origins. Our data indicated, in both genes, a clustering of the breakpoints in regions designated ELE1-bcr (1.8 kb) and RET-bcr (1.9 kb). Notably, in all sporadic tumors and in one post-Chernobyl tumor the ELE1/RET recombination corresponded with short sequences of homology (3-7 nt) between the two rearranging genes. In addition, we observed an interesting distribution of the post-Chernobyl breakpoints in ELE1-bcr located within an Alu element, or in between two close Alu elements, and always in A+T-rich regions.
Bongarzone
I
I
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
Butti
M G
MG
Fugazzola
L
L
Pacini
F
F
Pinchera
A
A
Vorontsova
T V
TV
Demidchik
E P
EP
Pierotti
M A
MA
D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000235:genetics*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D015321:Gene Rearrangement / Q000528:radiation effects; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009857:Oncogenes / Q000528:radiation effects; D016133:Polymerase Chain Reaction; D018788:Radioactive Hazard Release; D011995:Recombination, Genetic / Q000528:radiation effects; D013964:Thyroid Neoplasms / Q000235:genetics*; D014455:Ukraine
D017931:DNA Primers; D004273:DNA, Neoplasm