近日，美國Mayo Clinic的研究人員證明了整個染色體數量的改變，也就是非整倍性能夠導致癌症這一理論。他們的這項研究結果發表在最近一期的Cancer Cell上，文章對癌症研究領域的主要觀點，即是否非整倍體是癌症的成因做了詳細的論證。
事實上，所有的人類癌症都有異常的染色體數量。因此，存在這樣的一個長期猜測，基因變異導致細胞分裂過程中錯誤的染色體分離，這是腫瘤發生的主要原因。然而，由於試驗限制使得這一理論很難被證實。
這項研究的負責人Jan van Deursen博士介紹說，他們的實驗室使用一種新建立的人類腫瘤老鼠模型，對非整倍性導致癌症這一理論進行證實，並詳細解釋了該機制。
研究人員在文章中詳細解釋了染色體異常如何導致癌症，此外，他們還證明了染色體非整倍性在抑癌基因排除方面的作用。
非整倍性導致癌症的機制的證實，將更易於建立在這個理論基礎上的科學研究，並有可能產生新的藥物靶標。（生物谷Bioon.com）
生物谷推薦原始出處：
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.