Structural analysis of PAX3 genomic rearrangements in alveolar rhabdomyosarcoma
Structural analysis of PAX3 genomic rearrangements in alveolar rhabdomyosarcoma
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DOI：
10.1016/s0165-4608(97)00287-2
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发表时间：
1998-04-01
影响因子：
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通讯作者：
Hollows, JC
中科院分区：
文献类型：
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作者：
Barr, FG;Nauta, LE;Hollows, JC
在小儿腺泡状横纹肌肉瘤中，（2;13）（q35;q14）易位使PAX 3和FKHR并置，产生PAX 3-FKHR嵌合基因。使用Southern印迹方法，PAX 3内含子7的基因组重排检测到23融合阳性的23个腺泡型横纹肌肉瘤和未检测到在19个融合阴性的胚胎型横纹肌肉瘤。在23例PAX 3-FKHR阳性病例中，有21例检测到对应于FKHR-PAX 3相互融合的重排，但在23例病例中仅15例检测到FKHR-PAX 3转录本。定位实验表明，断点发生在整个17.5 kb的PAX 3内含子，并在23例中的12例，断点聚集在一个4.5 kb的区域内的3'端的内含子。染色质分析显示在内含子的5'端有一个明显的DNase I超敏位点，但没有发现任何其他可能影响断点分布的DNA-蛋白质相互作用。序列分析鉴定了3'簇内富含AT的区域，以及在该簇的边界处交替的嘌呤-嘧啶和高嘧啶元件。这些发现表明，易位断裂点被限制到PAX 3内含子7主要是由功能边界相关的侧翼外显子，并可能其次影响该内含子内的序列特征。(C)Elsevier Science Inc.，1998.
In the pediatric cancer alveolar rhabdomyosarcoma, the (2;13)(q35;q14) translocation juxtaposes PAX3 and FKHR to produce a chimeric PAX3-FKHR gene. With the use of Southern blot methodology, genomic rearrangements of PAX3 intron 7 were detected in 23 of 23 fusion-positive alveolar rhabdomyosarcomas and were not detected in 19 fusion-negative embryonal rhabdomyosarcomas. Rearrangements corresponding to the reciprocal FKHR-PAX3 fusion were detected in 21 of 23 PAX3-FKHR-positive cases, though FKHR-PAX3 transcripts were detected in only 15 of 23 cases. Mapping experiments demonstrated that breakpoints occurred throughout this 17.5 kb PAX3 intron and, in 12 of 23 cases, breakpoints clustered within a 4.5-kb region at the 3' end of the intron. Chromatin analysis revealed a prominent DNase I hypersensitive site at the 5' end of the intron but did not indicate any other DNA-protein interactions that might have affected the breakpoint distribution. Sequence analysis identified AT-rich regions within the 3' cluster, as well as alternating purine-pyrimidine and homopyrimidine elements at the borders of this cluster. These finding suggest that translocation breakpoints are constrained to PAX3 intron 7 primarily by functional boundaries related to the flanking exons and may be secondarily affected by sequence features within this intron. (C) Elsevier Science Inc., 1998.