APC allele-specific expression in carriers of Ashkenazi Jewish mutation I1307K

e22181 Background: I1307K is a missense APC variant with incomplete penetrance that has been found in 6% of Jewish Ashkenazi population and confers a two-fold increased risk to develop multiple adenomas and colorectal tumours. It is believed that it creates a hypermutable region within the gene that leads to an accumulation of mutations. It remains unknown whether the presence of this mutation modifies APC expression. Our goal was to study whether allele-specific expression (ASE) of I1307K is present at the germline and tumoral level. Methods: Paired germline/carcinoma RNA and DNA was studied from eleven I1307K carriers. To analyze changes in the mutant/wt allelic ratio we used single nucleotide primer extension (SNuPE) for the I1307K and the rs2229992 APCcoding SNP. Fourteen controls were also analyzed. Results: No germline allele specific expression was found in I1307K carriers (range=0.954–1.173). Significant ASE was observed in 8 of the 10 carcinomas analyzed. In 4 cases the I1307K allele was overexpr...