tumoursuppressorgener

Tumour suppressor genes are genes that encode proteins that regulate cell growth, promote DNA repair, and maintain genomic stability. They act to prevent uncontrolled cell division and tumor development by enforcing cell cycle checkpoints, inducing apoptosis in damaged cells, and influencing senescence. Loss or inactivation of these genes can remove critical safeguards against cancer, allowing cells to accumulate mutations and proliferate.

Most tumor suppressor gene dysfunction follows the two-hit model: both gene copies must be inactivated for loss of function. Individuals with germline pathogenic variants have a higher baseline risk and typically acquire a somatic second hit in susceptible cells. In sporadic cancers, both alleles are often hit somatically. In many cases, silencing by promoter methylation or gene deletion also reduces function.

Functional categories include cell cycle control (for example RB1, CDKN2A), DNA repair (TP53, BRCA1/BRCA2, MLH1, MSH2), and signal transduction or apoptosis (PTEN, VHL). Classic examples include TP53, RB1, BRCA1/BRCA2, APC, PTEN, and VHL. The TP53 gene encodes p53, a transcription factor that promotes DNA repair, cell-cycle arrest, or apoptosis after damage; BRCA1/BRCA2 are essential for homologous recombination repair; APC is linked to colorectal cancer when lost; PTEN antagonizes PI3K/AKT signaling.

Clinical relevance: Germline mutations underlie several hereditary cancer syndromes (e.g., Li-Fraumeni from TP53 and familial adenomatous polyposis from APC). Tumor suppressor gene status also informs therapy; PARP inhibitors exploit BRCA1/BRCA2 deficiency via synthetic lethality; research explores restoring p53 function as a cancer treatment. Genetic testing and risk assessment are common components of precision oncology.