Gene position within chromosome territories correlates with their involvement in distinct rearrangement types in thyroid cancer cells.

Gene position within chromosome territories correlates with their involvement in distinct rearrangement types in thyroid cancer cells.
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DOI:
10.1002/gcc.20639
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发表时间:
2009-03
影响因子:
3.7
通讯作者:
Nikiforov, Yuri E.
Nikiforov, Yuri E.
中科院分区:
医学2区
文献类型:
--
作者:
Gandhi, Manoj S.;Stringer, James R.;Nikiforova, Marina N.;Medvedovic, Mario;Nikiforov, Yuri E.

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人类癌症中的染色体重排有两种类型:染色体间重排(涉及位于不同染色体上的基因座之间的交换)和染色体内重排(涉及位于同一染色体上的基因座之间的重排)。通常激活特定癌基因的重排类型可能会受到其核位置及其伴侣的影响。在间期细胞核中,每条染色体占据一个独特的三维区域,该区域往往不与其他染色体的区域重叠。还已知基因组双链断裂后,游离 DNA 末端的活动性受到限制。这些考虑表明,位于染色体区域深处的基因座可能不像参与染色体内重排那样容易参与染色体间重排。为了检验这一假设,我们使用荧光原位杂交和 3D 高分辨率共聚焦显微镜来分析已知在人类癌细胞中通过重组激活的六种癌基因的位置。我们发现,与涉及染色体内倒位的基因座相比,涉及染色体间重排的基因座更靠近染色体区域的外围。这项研究的结果提供的证据表明,核结构和染色体区域内特定遗传位点的位置可能会影响它们参与人类甲状腺细胞的染色体内或染色体间重排。
Chromosomal rearrangements in human cancers are of two types, interchromosomal, which are rearrangements that involve exchange between loci located on different chromosomes, and intrachromosomal, which are rearrangements that involve loci located on the same chromosome. The type of rearrangement that typically activates a specific oncogene may be influenced by its nuclear location and that of its partner. In interphase nuclei, each chromosome occupies a distinct three-dimensional territory that tends to not overlap the territories of other chromosomes. It is also known that after double strand breaks in the genome, mobility of free DNA ends is limited. These considerations suggest that loci located deep within a chromosomal territory might not participate in interchromosomal rearrangements as readily as in intrachromosomal rearrangements. To test this hypothesis, we used fluorescence in situ hybridization with 3-D high-resolution confocal microscopy to analyze the positions of six oncogenes known to be activated by recombination in human cancer cells. We found that loci involved in interchromosomal rearrangements were located closer to the periphery of chromosome territories as compared to loci that were involved in intrachromosomal inversions. The results of this study provide evidence suggesting that nuclear architecture and location of specific genetic loci within chromosome territories may influence their participation in intrachromosomal or interchromosomal rearrangements in human thyroid cells.
在鱼类实验中保存大规模染色质结构。
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发表时间: 2006-04-13
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