Unbalanced translocation, a major chromosome alteration causing loss of heterozygosity in human lung cancer
Unbalanced translocation, a major chromosome alteration causing loss of heterozygosity in human lung cancer
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DOI：
10.1038/onc.2008.113
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发表时间：
2008-08-14
期刊：
影响因子：
8
通讯作者：
Yokota, J.
中科院分区：
文献类型：
--
作者：
Ogiwara, H.;Kohno, T.;Yokota, J.
杂合性丢失（LOH）是人类致癌过程中导致肿瘤抑制基因失活的主要遗传事件。为了阐明导致 LOH 的染色体机制，通过整合阵列比较基因组杂交获得的 DNA 拷贝数变化断点信息以及光谱核型分析获得的染色体数量和结构改变的信息，对通过全基因组单核苷酸多态性阵列分析检测到的 10 例人类肺癌中的 201 个 LOH 进行了研究，以了解负责的染色体改变。大多数（80%）的LOH是由染色体结构改变引起的部分染色体LOH，而其余（20%）是由全染色体缺失引起的全染色体LOH。不平衡易位被定义为最常见的改变，占所有 LOH 的 30%。其他三种结构改变——间质缺失（19%）、有丝分裂重组（9%）和基因转换（6%）——也导致了 LOH 的发生，而末端缺失仅导致了一小部分（1%）。由于不平衡易位是肺癌细胞中常见的染色体改变，因此本研究的结果强烈表明，在肺癌细胞中检测到的 LOH 中有相当一部分是由不平衡易位引起的。
Loss of heterozygosity (LOH) is a major genetic event causing inactivation of tumor suppressor genes in human carcinogenesis. To elucidate chromosomal mechanisms causing LOH, 201 LOHs in 10 cases of human lung cancer, which were detected bya genome-wide single nucleotide polymorphism array analysis, were investigated for responsible chromosome alterations by integrating information on breakpoints for DNA copy number changes obtained by array-comparative genome hybridization and on numerical and structural chromosomal alterations obtained by spectral karyotyping. The majority(80%) of LOHs were partial chromosome LOHs caused by structural chromosomal alterations, while the remaining (20%) were whole chromosome LOHs caused by whole chromosome deletions. Unbalanced translocation was defined as the most frequent alteration, and it accounted for 30% of all LOHs. Three other structural alterations-interstitial deletion (19%), mitotic recombination (9%) and gene conversion (6%)-also contributed to the occurrence of LOH, while terminal deletion contributed to only a small subset (1%). Since unbalanced translocation is a common chromosomal alteration in lung cancer cells, the results in the present study strongly indicate that a considerable fraction of LOHs detected in lung cancer cells are caused by unbalanced translocation.