Cancer is, in essence, a genetic disease caused by mutations in critical genes governing cell growth. Some mutations can be inherited, but the vast majority are acquired as somatic mutations during the progression from normal to cancer cell. Activating mutations affect genes that stimulate cell division (oncogenes), and inactivating mutations affect genes that normally prevent cell division (tumor suppressor genes). Finding and understanding the mutated genes that cause cancer is extremely important for the development of novel methods for early tumor detection, improved diagnosis, and targeted cancer chemotherapy. Cancer drugs that inhibit specific oncogenes are already in clinical use for treatment of some leukemias and solid tumors.
A fundamental problem has been the lack of comprehensive knowledge of the set of mutated genes that cause common solid tumors. A handful of frequently mutated genes and molecular pathways have been identified over the last decades using conventional molecular genetics. However, it is likely that these frequently mutated genes constitute the tip of an iceberg mainly composed of less frequently mutated genes that are much harder to identify by conventional means.
The human genome sequencing effort has in principle enabled a comprehensive and unbiased approach to cancer genetics, in the sense that all genes in a malignant tumor can be subjected to mutational analysis. We have previously conducted such a mutational analysis of 18,000 genes in breast and colorectal cancers. By sequencing these genes in 11 breast cancers and 11 colorectal cancers and comparing the sequences to those from matched normal tissues, we could identify 280 genes as likely involved in the development of these two diseases. One third of these genes had previously been implicated in cancer, but two thirds had not earlier been connected to malignant disease. Moreover, we could demonstrate that a typical late breast or colorectal cancer has somatic mutations in ~80-100 genes, and that ~14-20 of these genes are likely to be involved in disease development.
Research activities of the group include: