Molecular Cancer Genetics in Eastern and Central Europe

Over the last 10 years 25 different hereditary cancer syndromes have been identified and attributed to specific germline mutations in various inherited cancer genes. Though hereditary cancer syndromes are rare, their investigation has begun to provide unprecedented insights into the molecular origin and pathogenesis of various forms of cancer [3]. With the cloning of cancer-predisposing genes it has become possible to offer predictive DNA testing to family members at risk. For some well-defined, but uncommon inherited cancer syndromes (FAP, MEN2A, Retinoblastoma, VHL and Neurofibromatosis 1 and 2) genetic testing for cancer susceptibility is already part of the clinical management of families affected with cancer. For those inherited cancer syndromes where the risks associated with a predisposing mutation are less certain or effectiveness of preventive strategies are not confirmed, the use of genetic testing for cancer risk is not without controversies [11]. This second group includes the most common inherited cancer syndromes (such as hereditary breast cancers and hereditary non-polyposis colorectal cancers). At least five genes have been identified which may predispose to breast cancer. Germline mutations of BRCA1 and BRCA2 are thought to be responsible for the vast majority of inherited breast cancers [4]. Since the recent identification of BRCA1/BRCA2 genes [7,18], more than 600 distinct mutations in BRCA1 (and close to 600 in BRCA2) have been described (Breast Cancer Information Core (BIC) database: http://www.nhgri.nih.gov/Intramural_research/L ab_transfer/Bic/).