NGG · Next Generation Genetics of Cancer Predisposition

Unravelling genetic components of human tumor predisposition has contributed significantly to our understanding on molecular basis of cancer, and cancer prevention in the context of hereditary tumor susceptibility is one of the early examples of benefits from genetic disease information. Research into cancer susceptibility is of great importance, and as shown in this proposal Finland provides unique interdisciplinary possibilities to take the field forward. Indeed, in the near future ability to recruit very small groups of patients with a potentially novel cancer susceptibility phenotype will be more relevant than ever. Such materials have been resistant to previous gene identification approaches but lend themselves towards success by exomic and whole genome sequencing.Important discoveries are anticipated in the following fields of research to be conducted under NGG:1) Identification of rare high-penetrance Mendelian cancer predisposition conditions, and the respective susceptibility genes. One should note that the impact of a gene discovery for basic understanding of key cellular processes is not related to the frequency of the predisposition condition (e.g. RB, LKB1, P53 etc).2) Identification of moderate penetrance cancer susceptibility genes. Such phenotypes have been difficult to approach with traditional gene identification methods because large pedigrees with multiple affected individuals and few or no phenocopies are not easily identified. Also, the current GWAS approaches are not ideal to detect these loci due to relative rarity of the responsible variants.3) Characterization of common variants associated with cancer susceptibility.