Nikiforova M N, Stringer J R, Blough R, Medvedovic M, Fagin J A, Nikiforov Y E
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Science. 2000 Oct 6;290(5489):138-41. doi: 10.1126/science.290.5489.138.
Rearrangements involving the RET gene are common in radiation-associated papillary thyroid cancer (PTC). The RET/PTC1 type of rearrangement is an inversion of chromosome 10 mediated by illegitimate recombination between the RET and the H4 genes, which are 30 megabases apart. Here we ask whether despite the great linear distance between them, RET and H4 recombination might be promoted by their proximity in the nucleus. We used two-color fluorescence in situ hybridization and three-dimensional microscopy to map the positions of the RET and H4 loci within interphase nuclei. At least one pair of RET and H4 was juxtaposed in 35% of normal human thyroid cells and in 21% of peripheral blood lymphocytes, but only in 6% of normal mammary epithelial cells. Spatial contiguity of RET and H4 may provide a structural basis for generation of RET/PTC1 rearrangement by allowing a single radiation track to produce a double-strand break in each gene at the same site in the nucleus.
涉及RET基因的重排在辐射相关的甲状腺乳头状癌（PTC）中很常见。RET/PTC1型重排是由RET和H4基因之间的非法重组介导的10号染色体倒位，这两个基因相距30兆碱基。在这里，我们要问的是，尽管RET和H4基因在染色体上的线性距离很远，但它们在细胞核中的接近程度是否会促进它们之间的重组。我们使用双色荧光原位杂交和三维显微镜来绘制间期细胞核内RET和H4基因座的位置。在35%的正常人甲状腺细胞和21%的外周血淋巴细胞中，至少有一对RET和H4基因并列，但在正常乳腺上皮细胞中只有6%。RET和H4基因在空间上的毗邻可能为RET/PTC1重排的产生提供了结构基础，因为它允许单个辐射轨迹在细胞核的同一位置对每个基因产生双链断裂。
