In conclusion, this thesis describes several new insights into polyposis, particularly MUTYH-associated polyposis. This recessive inheritable disease represents approximately 10-20% of all... Show moreIn conclusion, this thesis describes several new insights into polyposis, particularly MUTYH-associated polyposis. This recessive inheritable disease represents approximately 10-20% of all polyposis patients with a wide variety in the phenotype and significant genotype-phenotype correlations. Organ systems outside the gastrointestinal tract seem to be relatively spared in MAP patients. Colorectal carcinoma in MAP patients have some specific molecular and histological features, which are similar to MSI-high and Lynch-associated CRCs, such as a preferential proximal location, mucinous histotype, and increased presence of TILs. These TILs could be associated with higher activated immune response, which leads to reduced tumour growth and reduced metastasis. Indeed, better survival in MAP carcinomas was found in a European MAP cohort. Furthermore, it was shown that APC deletion and APC mosaicism represent a substantial number of the discovered APC mutations. The remaining APC and MUTYH negative polyposis patients might have the following: mutations in high penetrance CRC associated genes that are yet to be discovered, mutations in non-scanned parts of the MUTYH or APC genes, or a combination of low penetrance alleles. Show less
