Identification and functional characterization of genetic cancer risk variants

Genome-wide association studies have led to the discovery of single nucleotide polymorphisms (SNPs) that associate with risk of various types of cancer, however, their functional role has in very few cases been characterized. The major objective of this Industry-Academia Partnership and Pathways (IAPP) project are 1) to discover and validate low-medium frequency polymorphisms that predispose to cancer using population genomics approach on one hand and SNP/mutation screening of panels of tumor/normal samples on the other; 2) to functionally validate the newly identified variants in human cells, using a variety of state of the art technologies, including somatic knock-in technology and 3) to throw light on biological properties associated with the known prostate cancer risk alleles at 8q24 using a combination of microarray and cytogenetic approaches.

This partnership brings together three groups which have hitherto focused on different aspects of cancer genetics. The major focus of deCODE genetics (deCODE) is to identify genetic causes of common diseases, including all common types of cancer. The Laboratory of Molecular Genetics at the Dept. of Oncological Sciences, University of Torino (UNITO) has focused its studies on mutations in signal transduction pathways in tumors. Furthermore, the UNITO group has developed an innovative technology for knock-in of genetic variants in order to reconstruct genetic events in tumor progression. The Dept. of Oncology-Pathology at the Karolinska Insitute (OP-KI) OP-KI has developed a quantitative, multi-gene FISH-technique, referred to as QM-FISH, which enables the study of gene copy number changes (allelic imbalances) in clinical samples from tumors on a large-scale basis. By combining their technical and human resources, the partners aim to increase our knowledge about the mechanism by which germline variation affects carcinogenesis.