AbstractsBiology & Animal Science

Identification of novel epigenetic biomarkers in colorectal cancer

by Hilde Honne

Institution: University of Oslo
Year: 1000
Keywords: tykktarmskreft epigenetikk DNA metylering biomarkører; VDP::473
Record ID: 1277086
Full text PDF: https://www.duo.uio.no/handle/10852/11543



Colorectal cancer is a common malignancy that develops over a long period of time. Most cases are sporadic, while a small percentage is hereditary, such as hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome). There are two main molecular classifications of primary colorectal carcinomas, those with the microsatellite instability phenotype and those with chromosomal aberrations. In this study, we aimed to identify yet undiscovered genes targeted through hypermethylation of their promoter in each of the two subgroups of this disease. Furthermore, we wanted to determine whether the same methylation markers were found in other tumours of the types belonging to the HNPCC tumour spectrum. Seven of 13 novel candidate genes showed promoter hypermethylation in colorectal tumours, ranging from hypermethylation of 2% to 63% of the tumours. One isoform of the gene AK5 was hypermethylated in the majority of cases, whereas hypermethylation of the other AK5 isoform as well as the gene MTERF was specific for microsatellite unstable tumours. This adds two more markers to the set of known MSI identifiers. CRABP1, ADAMTS1, and NR3C1 displayed hypermethylation in gastric and endometrial tumours, in contrast to the urological cancers, supporting the hypothesis that tumours of the HNPCC spectrum share many of the same molecular events. However, the differences in methylation frequencies among the cancer types suggest that it is possible to combine a set of markers that distinguish among them if used in a future non-invasive test.