Preferential amplitication of AURKA 91A (Ile31) in familial colorectal cancers

In a previous genome-wide effort we identified a novel candidate colorectal cancer (CRC) susceptibility locus by allelotyping tumors from familial and sporadic CRC patients. Familial cases harbored amplifications significantly more frequently in 20q13, indicating the presence of a putative oncogene within the amplicon. A kinase-encoding A URKA is, located in 20q13 and recently a Phe31Ile (91T>A) change of AURKA was suggested to function as a low penetrance tumor-susceptibility factor. Association analysis suggested an increased cancer risk in 91A homozygous individuals. In addition, tumors from heterozygous individuals showed preferential amplification of 91A allele and were more aneuploid, important findings that have not been confirmed to date. To evaluate whether AURKA is a target for the observed 20q13 amplifications, we assessed the frequency of the 91T>A change and possible preferential amplification of either allele in 125 familial and 110 sporadic Finnish CRC cases. We observed a preferential amplification of 91A with a significant difference between the alleles in the familial group (p = 0.03). Furthermore, a trend between younger age at diagnosis and genotype in the familial group was observed (p = 0.06). Other possible AURKA germline variants were screened by sequencing 10 of the familial cases. The frequency and amplification patterns of the observed variants were assessed in a larger set of familial and sporadic CRC but no evidence on tumorigenic role of the other sequence alterations was obtained. Thus our results support the importance of AURKA 91A as a low penetrance CRC susceptibility factor. (c) 2005 Wiley-Liss. Inc.