来自瑞典卡罗林斯卡医学院和芬兰赫尔辛基大学的研究人员发现在人类全基因组关联研究中鉴定到的一个单核苷酸多态性(SNP)rs6983267(已知能增加人类癌症风险),能够影响小鼠的肿瘤发生。这项研究有助于人类癌症的防治。

-2012年12月7日《科学》

中文翻译


【题目】缺乏Myc增强子的小鼠能够抵抗肠道肿瘤

【译文】 研究已证实在人类染色体8q24上的MYC原癌基因上游50万碱基区域内的保守序列中有大量的癌症相关单核苷酸多态性(SNPs)。这些SNPs可能通过影响MYC基因的表达调控来影响癌症的发育,但是这一假设难以验证。我们成功获得了Myc-335缺陷小鼠,Myc-335蛋白的编码基因是一个假定的MYC调控元件,包含rs6983267,这个SNP能解释为什么个体含有这个SNP会比其他的遗传变异体或突变具有更高的人类癌症相关的发病率。在Myc-335缺陷小鼠中,Myc基因在肠隐窝中表达其转录产物,表达模式类似野生型小鼠,但转录产物的含量小幅降低。突变小鼠没有表现出明显的表型,但却能显著地抵抗APCmin基因突变诱导的肠道肿瘤发生。这些结果证实人类全基因组关联研究中鉴定到的癌症相关的SNP在体内具有一定的功能效应。

英文原稿


[Title]: Mice Lacking a Myc Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors    

[Authors]: Inderpreet Kaur Sur, Outi Hallikas, Anna Vähärautio, Jian Yan, Mikko Turunen, Martin Enge, Minna Taipale, Auli Karhu, Lauri A. Aaltonen, and Jussi Taipale

[Abstract]: Multiple cancer-associated single-nucleotide polymorphisms (SNPs) have been mapped to conserved sequences within a 500-kilobase region upstream of the MYC oncogene on human chromosome 8q24. These SNPs may affect cancer development through altered regulation of MYC expression, but this hypothesis has been difficult to confirm. We generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer-related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype but were markedly resistant to intestinal tumorigenesis induced by the APCmin mutation. These results establish that a cancer-associated SNP identified in human genome-wide association studies has a functional effect in vivo.

原文地址

http://www.sciencemag.org/content/338/6112/1360.abstract

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