Polygenic control of hepatocarcinogenesis in Copenhagen X F344 rats
Polygenic control of hepatocarcinogenesis in Copenhagen X F344 rats
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DOI：
10.1002/ijc.20225
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发表时间：
2004-08-10
影响因子：
6.4
通讯作者：
Feo, F
中科院分区：
文献类型：
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作者：
De Miglio, MR;Pascale, RM;Feo, F
(1)Cop和CFFI大鼠表现出对肝癌发生的抗性，与肿瘤病变的高重塑率相关。我们在雄性CFF2大鼠中绘制了影响“耐药肝细胞”模型诱导的肿瘤结节数量、体积和体积分数的肝癌易感性、耐药和重塑位点。在染色体1、4和18上发现了3个与非重塑病变数量或体积有显著连锁关系的位点。在染色体1、2、1:3、14和15上发现了7个位点与总、非重塑或重塑病变的数量或体积分数有关联。这些位点对表型性状均有显著的等位基因特异性影响。通过方差分析，我们还发现了19个双向相互作用，这些相互作用诱导的表型效应在单独效应的基础上是不可预测的。这些新的上位性位点与总、非重塑或重塑结节的数量和/或体积有显著的联系。这些数据表明，Cop大鼠对肝癌发生的易感性是由一系列复杂的基因控制的，这些基因具有多种基因相互作用，不同的遗传机制控制着重塑和非重塑的肝结节。在人类肝癌中，位于与大鼠易感/耐药位点同属的染色体片段上的基因经常解除管制，这表明大鼠和人类肝癌发生的遗传机制存在一些相似之处。(C) 2004 Wiley-Liss, Inc。
(1)Cop and CFFI rats exhibit resistance to hepatocarcinogenesis, associated with high rates of remodeling of neoplastic lesions. We have mapped hepatocarcinogenesis susceptibility, resistance and remodelling loci affecting the number, volume and volume fraction of neoplastic nodules induced by the "resistant hepatocyte" model in male CFF2 rats. Three loci in significant linkage with the number or volume of nonremodeling lesions were identified on chromosomes 1, 4 and 18. Suggestive linkage with number or volume fraction of total, nonremodeling or remodeling lesions was found for 7 loci on chromosomes 1, 2, 1:3, 14 and 15. All of these loci showed significant allele-specific effects on the phenotypic traits. We also detected by analysis of variance 19 2-way interactions inducing phenotypic effects not predictable on the basis of the sum of separate effects. These novel epistatic loci were in significant linkage with the number and/or volume of total, nonremodeling or remodeling nodules. These data indicate that susceptibility to hepatocarcinogenesis in Cop rats is controlled by a complex array of genes with several gene-gene interactions and that different genetic mechanisms control remodeling and nonremodeling liver nodules. Frequent deregulation in human liver cancer of genes positioned in chromosomal segments syntenic to rat susceptibility/resistance loci suggests some similarities between the genetic mechanisms involved in hepatocarcinogenesis in rats and humans. (C) 2004 Wiley-Liss, Inc.