The term "Class II tumor suppressor gene" was already proposed in 1997 by Ruth Sager* (here is a tribute to her scientific life) after finding that many genes in a variety of human cancers rather showed strong down regulation (compared to healthy tissue) than being altered by mutation or deletion.
Class II Tumor Suppressor Genes (C2TSGs) usually have a role in negatively regulating cell growth, e.g. by reducing proliferation, supporting apoptosis or differentiation or inhibiting invasion. Thus tumor cells seek to regulate down these important genes. In a BMBF-funded project which was part of the German Human Genome Project (DHGP), we have discovered and further characterized a larger number of new putative C2TSGs. The candidate genes were the result of a screening procedure in which EST cDNA libraries were screened for differentially expressed genes. A detailed description of the procedure can be found here*.
Starting from 600 genes which were found to be differentially expressed in gynecological tumors 40 particularly interesting candidate genes were selected, which were characterized in greater detail by the DHGP consortium "Genetic Basis of Gynaecological Carcinomas" (Dahl et al. Abstract*).
Later on our research group characterized further putative C2TSGs (and novel putative oncogenes) by molecular profiling of laser-microdissected matched tumor and normal breast tissues. (Abstract*)
Since down-regulation of C2TSGs in cancer is reversible in principle (there is no gene deletion or mutated allele present in the tumor cell), C2TSGs themselves and the pathways regulated by them may offer novel therapeutic approaches to combat cancer. (Abstract*)