近日，美国Mayo Clinic的研究人员证明了整个染色体数量的改变，也就是非整倍性能够导致癌症这一理论。他们的这项研究结果发表在最近一期的Cancer Cell上，文章对癌症研究领域的主要观点，即是否非整倍体是癌症的成因做了详细的论证。
事实上，所有的人类癌症都有异常的染色体数量。因此，存在这样的一个长期猜测，基因变异导致细胞分裂过程中错误的染色体分离，这是肿瘤发生的主要原因。然而，由于试验限制使得这一理论很难被证实。
这项研究的负责人Jan van Deursen博士介绍说，他们的实验室使用一种新建立的人类肿瘤老鼠模型，对非整倍性导致癌症这一理论进行证实，并详细解释了该机制。
研究人员在文章中详细解释了染色体异常如何导致癌症，此外，他们还证明了染色体非整倍性在抑癌基因排除方面的作用。
非整倍性导致癌症的机制的证实，将更易于建立在这个理论基础上的科学研究，并有可能产生新的药物靶标。（生物谷Bioon.com）
生物谷推荐原始出处：
Cancer Cell, Volume 16, Issue 6, 475-486, 8 December 2009 doi:10.1016/j.ccr.2009.10.023
Whole Chromosome Instability Caused by Bub1 Insufficiency Drives Tumorigenesis through Tumor Suppressor Gene Loss of Heterozygosity
Darren J. Baker1, Fang Jin1, Karthik B. Jeganathan1 and Jan M. van Deursen1, 2, ,
1 Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
2 Department of Molecular Biology and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Genetic alterations that promote chromosome missegregation have been proposed to drive tumorigenesis through loss of whole chromosomes containing key tumor suppressor genes. To test this unproven idea, we bred Bub1 mutant mice that inaccurately segregate their chromosomes onto p53+/−, ApcMin/+, Rb+/−, or Pten+/− backgrounds. Bub1 insufficiency predisposedp53+/− mice to thymic lymphomas and ApcMin/+ mice to colonic tumors. These tumors consistently lacked the nonmutated tumor suppressor allele but had gained a copy of the mutant allele. In contrast, Bub1 insufficiency had no impact on tumorigenesis in Rb+/− mice and inhibited prostatic intraepithelial neoplasia formation in Pten+/− mice. Thus, Bub1 insufficiency can drive tumor formation through tumor suppressor gene loss of heterozygosity, but only in restricted genetic and cellular contexts.
