Comparative analysis of cancer genes in the human and chimpanzee genomes.
Comparative analysis of cancer genes in the human and chimpanzee genomes.
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DOI：
10.1186/1471-2164-7-15
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发表时间：
2006-01-26
期刊：
影响因子：
4.4
通讯作者：
López-Otín C
中科院分区：
文献类型：
--
作者：
Puente XS;Velasco G;Gutiérrez-Fernández A;Bertranpetit J;King MC;López-Otín C
癌症是现代社会的主要医学问题。然而，这种疾病在非人类灵长类动物中的发病率非常低。为了研究人类和黑猩猩之间的遗传差异是否会导致他们不同的癌症易感性，我们在黑猩猩基因组中检测了一组333个人类癌症基因的直系同源基因。这项分析显示，所有检测的人类癌症基因都存在于黑猩猩中，包含完整的开放阅读框架，并显示出两个物种之间的高度保守性。然而，对这组基因的详细分析表明，与人类癌症特别相关的基因存在一些差异。因此，编码p53的黑猩猩基因在密码子72处含有Pro残基，而该密码子在人类中是多态性的，并且可以编码Arg或Pro，产生具有不同诱导细胞凋亡或与p73相互作用的能力的同种型。此外，BRCA1基因的测序显示黑猩猩序列中有一个8 Kb的缺失，过早地截断了共调节的NBR2基因。这些数据表明，癌症基因的微小差异，如肿瘤抑制基因中发现的差异，可能会影响人类和黑猩猩之间癌症易感性的差异。然而，需要进一步分析以确定本研究中确定的遗传变化对非人灵长类动物不同癌症发病率的确切贡献。
Cancer is a major medical problem in modern societies. However, the incidence of this disease in non-human primates is very low. To study whether genetic differences between human and chimpanzee could contribute to their distinct cancer susceptibility, we have examined in the chimpanzee genome the orthologous genes of a set of 333 human cancer genes. This analysis has revealed that all examined human cancer genes are present in chimpanzee, contain intact open reading frames and show a high degree of conservation between both species. However, detailed analysis of this set of genes has shown some differences in genes of special relevance for human cancer. Thus, the chimpanzee gene encoding p53 contains a Pro residue at codon 72, while this codon is polymorphic in humans and can code for Arg or Pro, generating isoforms with different ability to induce apoptosis or interact with p73. Moreover, sequencing of the BRCA1 gene has shown an 8 Kb deletion in the chimpanzee sequence that prematurely truncates the co-regulated NBR2 gene. These data suggest that small differences in cancer genes, as those found in tumor suppressor genes, might influence the differences in cancer susceptibility between human and chimpanzee. Nevertheless, further analysis will be required to determine the exact contribution of the genetic changes identified in this study to the different cancer incidence in non-human primates.
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.8
作者：
Dumont, P;Leu, JIJ;Murphy, M
通讯作者：
Murphy, M
影响因子：
64.5
作者：
Bond, GL;Hu, WW;Levine, AJ
通讯作者：
Levine, AJ
影响因子：
64.8
作者：
Gibbs, RA;Belmont, JW;Tanaka, T
通讯作者：
Tanaka, T
影响因子：
30.8
作者：
Balbín, M;Fueyo, A;López-Otín, C
通讯作者：
López-Otín, C