Genetic and epigenetic mechanisms of tumor predisposition in hereditary non-polyposis colorectal carcinoma and sporadic cancers

摘要: Approximately 70% of all colorectal cancers (CRCs) are sporadic, occurring by chance or due to environmental factors, and 25-30% have hereditary background. Hereditary CRC occurs at younger age (~ 45 years), compared sporadic (~70 years). Egyptian makes an exception the previous rule, since there 60 % patients diagnosed less than 50 years age. Individuals with inherited deficiency in DNA mismatch repair (MMR) (Lynch syndrome) LS predisposed different a non-random fashion. Endometrial cancer (EC) is most common extracolonic malignancy LS. represents best characterized form nonpolyposis carcinoma (HNPCC). Other forms familial non-polyposis colon exist, including type X (FCCX). This syndrome resembles LS, but MMR gene defects excluded predisposition genes unknown so far. To address why organs differently susceptible development, we examined molecular similarities differences selected whose frequency varies individuals. Tumors that (colorectal, endometrial, gastric) (brain, urological) were for protein expression, microsatellite instability (MSI), altered methylation. We also studied samples histologically normal endometrium, endometrial hyperplasia, alterations identify potential markers could predict malignant transformation cases. CRC, EC, gastric, uroepithelial showed MSI conventional methods, brain tumors did not show MSI. Also methylation Wnt-signalling pathway activation status distinguished kidney from gastric cancers, suggesting follow development related cancers. Our results suggest detectable tissues proportion mutation carriers prior development. Traditionally (complex) atypical hyperplasia has been considered critical progression malignancy. complex without atypia equally important as precursor lesion Tumor profiles Egypt Finland evaluate if specific ethnic origin (East vs. West). Results first time distinct genetic epigenetic signature marked high