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 different „Hallmarks of Cancer“, e.g. by reducing cell proliferation, supporting apoptosis or differentiation or inhibiting invasion and metastasis. Thus tumor cells seek to regulate down these important genes. Already more than 20 years ago, we have started to discover and further characterize a larger number of new putative C2TSGs by a screening procedure involving EST cDNA libraries. A 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 C2TSGs were selected, which were characterized in greater detail by the German Human Genome Project (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*) and by in silico analysis of databases like TCGA. (Abstract*)
(New abstract: Dehelean DC, Breitbach A, Hilgers L, Villwock S, Knüchel-Clarke R, Dahl E. Identifying novel class II tumor suppressor genes in breast cancer. In: Virtuelle Pathologietage Der Deutschen Gesellschaft Für Pathologie e.V. Abstractband; 2021:106-106.) (in German)
We characterize novel C2TSG candidates by their effect on tumor cell behavior after forced re-expression in different models of human cancer. A complete list of C2TSGs stably transfected in human cancer cell lines is available here. These cell lines are all available for scientific cooperations.
We are convinced that C2TSGs themselves and the pathways regulated by them may offer novel therapeutic approaches to combat cancer, as we have recently published in a white paper on this topic (https://www.mdpi.com/2072-6694/14/18/4386).