APC mutation spectrum in ileoanal pouch polyps resembles that of colorectal polyps

Abstract Background Ileoanal pouch polyps commonly develop following restorative proctocolectomy in patients with familial adenomatous polyposis (FAP). In FAP adenomas, the relationship between germline and somatic adenomatous polyposis coli (APC) mutations is determined by ‘just right’ β-catenin signalling in tumour cells, with respect to the 20-amino acid β-catenin-binding/degradation repeats (20AARs) in the APC protein. However, the relationship varies, with upper gastrointestinal polyps typically retaining three to four 20AARs and colonic polyps retaining one or two. The aim of this study was to establish the mutational spectrum in ileoanal pouch polyps, to ascertain whether polyp development resembled that typical of small or large bowel. Methods Some 151 pouch adenomas were screened from 46 patients with known germline APC mutations for ‘second hits’ acquired through loss of heterozygosity and truncating mutations. The number of 20AARs remaining after the ‘second hit’ was calculated. Results Loss of heterozygosity was rare in pouch polyps except when the germline mutation left one 20AAR. Overall, the combined alleles left two to three 20AARs in 40 of 51 polyps with an identified ‘second hit’. This was significantly fewer than in upper gastrointestinal polyps, and more than in colorectal adenomas. Conclusion Tissue environment appears to influence the position of the ‘second hit’ in pouch polyps and the mutations resemble those of large bowel polyps.