The breakpoint region of the most common isochromosome, i(17q), in human neoplasia is characterized by a complex genomic architecture with large, palindromic, low-copy repeats
The breakpoint region of the most common isochromosome, i(17q), in human neoplasia is characterized by a complex genomic architecture with large, palindromic, low-copy repeats
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DOI：
10.1086/380648
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发表时间：
2004-01-01
影响因子：
9.8
通讯作者：
Fioretos, T
中科院分区：
文献类型：
--
作者：
Barbouti, A;Stankiewicz, P;Fioretos, T
尽管已经积累了大量关于与遗传性疾病相关的DNA结构重排的机制的信息，但实际上对与获得性肿瘤相关的染色体重排所涉及的分子过程一无所知。等染色体 17q 或“i( 17q)”是人类肿瘤中最常见的结构异常之一。我们之前在 17p11.2 中确定了 i(17q) 形成的断点聚类区域，并假设基因组结构特征可能是造成这种聚类的原因。为了解决这一假设，我们精确绘制了 11 名患有不同血液恶性肿瘤的患者的 i(17q) 断点，并确定了相关区域的基因组结构。我们的结果揭示了 i(17q) 断点簇区域中复杂的基因组结构，其特征是大（类似于 38-49-kb）、回文、低拷贝重复，强烈表明体细胞重排不是随机事件，而是反映了基因组结构引起的易感性。
Although a great deal of information has accumulated regarding the mechanisms underlying constitutional DNA rearrangements associated with inherited disorders, virtually nothing is known about the molecular processes involved in acquired neoplasia-associated chromosomal rearrangements. Isochromosome 17q, or "i( 17q)," is one of the most common structural abnormalities observed in human neoplasms. We previously identified a breakpoint cluster region for i(17q) formation in 17p11.2 and hypothesized that genome architectural features could be responsible for this clustering. To address this hypothesis, we precisely mapped the i( 17q) breakpoints in 11 patients with different hematologic malignancies and determined the genomic structure of the involved region. Our results reveal a complex genomic architecture in the i( 17q) breakpoint cluster region, characterized by large (similar to 38 - 49-kb), palindromic, low-copy repeats, strongly suggesting that somatic rearrangements are not random events but rather reflect susceptibilities due to the genomic structure.