Cel We focus on hereditary cancers of the digestive system associated with microsatellite instability, hereditary non-polyposis colorectal cancer (HNPCC) and familial gastric cancer (FGC). Microsatellite instability is the result of a defective mismatch repai r (MMR) system. Germline mutations in MMR genes are found in families with HNPCC, characterised by development of colorectal cancer and extracolonic malignancies, particularly cancer of the endometrium. Evidence is accumulating that also a subset of FGC i s MMR-related as families have been identified with tumours showing microsatellite instability. MMR gene mutations have not yet been identified in these families. In HNPCC, identification of MMR gene mutations has helped in identifying individuals at risk when a clear pathogenic mutation was found. Many families, however, in particular those with less penetrant HNPCC, remain genetically unresolved. Furthermore, in a large proportion of families mutations are identified whose pathogenic nature is uncertain (unclassified variants). Although we have made great progress in the genetic delineation of this cancer syndrome, it has hardly improved early diagnosis or treatment of cancer. To improve genetic testing we will (1) determine the role that known MMR genes play in both cancer syndromes and identify new MMR-related genes underlying HNPCC or FGC; (2) set up comprehensive functional assays to determine the role of unclassified variants in MMR related genes; (3) identify tumour cells at very early stages in faec es by enhancing the sensitivity of MSI determination; (4) profile mutations accumulating in tumours as a consequence of MMR deficiency in order to get a better insight in tumour development, which can be instrumental in clinical management/tumour treatment . Our proposal will thus improve genetic testing, improve early detection of polyps/tumours in individuals at risk for these cancer syndromes and improve clinical management of HNPCC and FGC patients. Dziedzina nauki natural sciencescomputer and information sciencesdatabasesmedical and health sciencesclinical medicineoncologycolorectal cancernatural sciencesbiological sciencesgeneticsmutation Program(-y) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Temat(-y) LSH-2004-2.2.0-6 - Prevention, detection and treatment of familial cancers, such as cancer of the prostate, ovary, breast, colon and skin LSH-2004-2.3.0-1 - Development of new HIV/AIDS vaccine approaches Zaproszenie do składania wniosków FP6-2004-LIFESCIHEALTH-5 Zobacz inne projekty w ramach tego zaproszenia System finansowania STREP - Specific Targeted Research Project Koordynator UNIVERSITY HOSPITAL GRONINGEN Wkład UE Brak danych Adres Hanzeplein 1 GRONINGEN Niderlandy Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych Uczestnicy (4) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko HELSINGIN YLIOPISTO Finlandia Wkład UE Brak danych Adres Yliopistonkatu 4 HELSINGIN YLIOPISTO, HELSINKI Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych ROSKILDE UNIVERSITETSCENTER Dania Wkład UE Brak danych Adres Universitetsvej 1, Building 18-1 ROSKILDE Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych LEIDEN UNIVERSITY MEDICAL CENTER Niderlandy Wkład UE Brak danych Adres Albinusdreef 2 LEIDEN Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych INSTITUTO DE PATOLOGIA E IMUNOLOGIA MOLECULAR DA UNIVERSIDADE DO PORTO Portugalia Wkład UE Brak danych Adres RUA ROBERTO FRIAS S/N PORTO Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych