近日，美國(guó)Mayo Clinic的研究人員證明了整個(gè)染色體數(shù)量的改變，也就是非整倍性能夠?qū)е掳┌Y這一理論。他們的這項(xiàng)研究結(jié)果發(fā)表在zui近一期的Cancer Cell上，文章對(duì)癌癥研究領(lǐng)域的主要觀點(diǎn)，即是否非整倍體是癌癥的成因做了詳細(xì)的論證。

        事實(shí)上，所有的人類(lèi)癌癥都有異常的染色體數(shù)量。因此，存在這樣的一個(gè)長(zhǎng)期猜測(cè)，基因變異導(dǎo)致細(xì)胞分裂過(guò)程中錯(cuò)誤的染色體分離，這是腫瘤發(fā)生的主要原因。然而，由于試驗(yàn)限制使得這一理論很難被證實(shí)。

        這項(xiàng)研究的負(fù)責(zé)人Jan van Deursen博士介紹說(shuō)，他們的實(shí)驗(yàn)室使用一種新建立的人類(lèi)腫瘤老鼠模型，對(duì)非整倍性導(dǎo)致癌癥這一理論進(jìn)行證實(shí)，并詳細(xì)解釋了該機(jī)制。

        研究人員在文章中詳細(xì)解釋了染色體異常如何導(dǎo)致癌癥，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(dǎo)致癌癥的機(jī)制的證實(shí)，將更易于建立在這個(gè)理論基礎(chǔ)上的科學(xué)研究，并有可能產(chǎn)生新的藥物靶標(biāo)。

上海勁馬生物推薦原始出處：

Cancer Cell, Volume 16, Issue 6, 475-486, 8 December 2009 doi:10.1016/r.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 inaccuray segregate their chromosomes onto p53^+/−, Apc^Min/+, Rb^+/−, or Pten^+/− backgrounds. Bub1 insufficiency predisposedp53^+/− mice to thymic lymphomas and Apc^Min/+ 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.