Although cancer is fundamentally a genetic disease, in the majority of cancers the mutations occur somatically (i.e., only in the tissue from which the cancer is derived). However, for many types of cancer, for example, breast, ovarian, and colorectal cancer there are a small number of cases that arise because of an inherited germline mutation. Genetic linkage analysis of such families enables the likely location of the TSG to be determined and has proven very successful in cloning some important TSGs. However, the genes responsible for inherited predisposition to cancer represent only a fraction of the total number of genetic defects that underlie the disease process.