Ewart-Toland et al. (2003) performed association studies using DNA samples from individuals of northern European ancestry with cancer and matched controls and identified a single SNP that appeared to play a role susceptibility to colon cancer: a T-to-A transversion at position 91 in the AURKA (STK15) coding sequence that resulted in a phe31-to-ile (F31I) substitution. Based on their observation that Aurka in the mouse is a strong candidate gene located in a tumor susceptibility QTL and that it shows evidence of allele-specific changes in mouse tumors, Ewart-Toland et al. (2003) investigated the possibility that allele-specific amplification of the 91A allele of AURKA (encoding the ile31 variant) might also occur in human tumors. The results showed statistically significant allele-specific amplification of the 91A allele in genotyping of DNA samples from 162 individuals for whom both normal colon mucosa and colon tumor DNA was available. The possibility that the results were explained by another gene in linkage disequilibrium (LD) with AURKA was considered highly unlikely, as LD in humans usually extends no more than 100 kb and the other candidate genes, such as ZNF217 (602967) and CYP24A1 (126065), are located much farther away than 100 kb.
The main role of AURKA in tumor development is in controlling chromosome segregation during mitosis (Bischoff and Plowman, 1999). Misregulation of this process results in aneuploidy, a distinctive feature of most cancers, which can be induced by overexpression of AURKA in cell lines (Zhou et al., 1998). Ewart-Toland et al. (2003) found that tumors from individuals carrying the 91A allele showed more evidence of aneuploidy than those from individuals who were homozygous for the common 91T allele. They concluded that individuals with even 1 copy of the AURKA 91A allele develop tumors that have on average a higher degree of aneuploidy than those from individuals homozygous for 91T.
