Nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas.
Nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas.
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遗传性和散发性肾细胞癌中的非同源染色单体交换。
DOI：
10.1073/pnas.88.1.194
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发表时间：
1991
影响因子：
11.1
通讯作者：
Kung,HF
中科院分区：
文献类型：
--
作者：
Kovacs,G;Kung,HF
在肾癌的发生发展过程中，有观点认为在同源染色体3p上发生胚系或体细胞突变，随后3p片段丢失。我们用限制性片段长度多态分析方法检测了2例von Hippel-Lindau病患者的28例肾癌患者的正常肾和肿瘤标本的核型和/或3号和5号染色体上的等位基因组合，并与散发性肿瘤进行了比较。染色体3p和5q或其他染色体之间的不平衡易位是最常见的异常。我们建立了一个涉及染色体3p13、3p11.2、5q22和8q11.2上的断裂点簇的非同源染色单体交换模型。随后的染色单体分离可能导致3p片段的净丢失，或者(I)在一步中，或者(Ii)在携带3p片段的衍生染色体的非分离丢失之后。这一一般机制也可以用来解释其他类型实体肿瘤中发生的基因变化。
For the development of renal cell carcinomas, it has been suggested that a germ-line or somatic mutation occurs on one of the homologous chromosomes 3p, and subsequently the other 3p segment is lost. We have examined the karyotype and/or the allelic combination on chromosomes 3 and 5 by restriction fragment length polymorphism analysis in normal kidney and tumor samples from 28 renal cell carcinomas that developed in two patients with von Hippel-Lindau disease; we then compared the results to those of sporadic tumors. An unbalanced translocation between chromosome 3p and 5q or other chromosomes was found to be the most common aberration. We developed a model of nonhomologous chromatid exchange involving breakpoint clusters at chromosomes 3p13, 3p11.2, 5q22, and 8q11.2. Subsequent chromatid segregation may result in net loss of the 3p segment either (i) in one step or (ii) after a nondisjunctional loss of the derivative chromosome carrying the 3p segment. This general mechanism could also be implicated to explain genetic changes occurring in other types of solid tumors.