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 farm of the RET protooncogene, w hich 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-associa ted post-Chernobyl tumors. To understand the molecular basis that pred isposes RET and ELE1 genes to be recurrent targets of ''illegitimate'' recombination, we examined the genomic regions containing the ELE1/RE T breakpoints of six sporadic and three post-Chernobyl tumors in two p apillary 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-Che rnobyl breakpoints in ELE1-bcr located within an Alu element, or in be tween two close Alu elements, and always in A+T-rich regions. (C) 1997 Academic Press.