Bongarzone I, Butti M G, Fugazzola L, Pacini F, Pinchera A, Vorontsova T V, Demidchik E P, Pierotti M A
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
Genomics. 1997 Jun 1;42(2):252-9. doi: 10.1006/geno.1997.4685.
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.
RET/PTC3致癌基因是RET原癌基因的一种激活形式，在甲状腺乳头状癌中经常发生重排。RET/PTC3是ELE1基因与RET基因之间结构重排的结果，在散发性肿瘤以及切尔诺贝利核事故后的辐射相关肿瘤中均有发现。为了了解使RET和ELE1基因易于成为“异常”重组反复靶向目标的分子基础，我们在两个不同来源的甲状腺乳头状癌中，检查了六个散发性肿瘤和三个切尔诺贝利核事故后肿瘤中包含ELE1/RET断点的基因组区域。我们的数据表明，在这两个基因中，断点均聚集在指定为ELE1-bcr（1.8 kb）和RET-bcr（1.9 kb）的区域。值得注意的是，在所有散发性肿瘤和一个切尔诺贝利核事故后肿瘤中，ELE1/RET重组与两个重排基因之间的短同源序列（3-7个核苷酸）相对应。此外，我们观察到切尔诺贝利核事故后ELE1-bcr中的断点呈现出有趣的分布，这些断点位于一个Alu元件内，或两个相邻Alu元件之间，并且总是位于富含A+T的区域。
