Tumor suppressor genes

A group of genes (and miRNAs) whose product are mainly negative regulators of cell division, controllers of DNA sustainability and signals for apoptosis. Tumor suppressor gene defects lead to cancer, but unlike proto-oncogenes, they generally follow the "Knudson two-hit hypothesis," which implies that both alleles that code for a particular protein must be affected before an oncogenic potential is manifested; they have a recessive effect.

Tumor suppressor genes are divided are classified as caretakers (that protect the integrity of the genome) and gatekeepers (that regulate/inhibit the cell cycle). In a cell, they represent:
 * Intracellular cell cycle inhibitors that regulate or inhibit specific stages of the cell life
 * Hormone receptors that inhibit cell proliferation
 * Checkpoint proteins that arrest the cell if DNA is damaged or improperly arranged in chromosomes
 * Proteins that promote apoptosis
 * Enzymes of DNA repair mechanisms

Defect in one allele can be inherited from a family member without any signs but increases the chance to acquire the second mutation on the somatic level and propagate cancer. Several cancer syndromes are attributed to tumor suppressor gene defects. These family pedigrees resemble autosomal dominant inheritance.

Cancer syndromes affect the same organs as sporadic cancers but typically come at younger age and bilaterally. Retinoblastoma (historically first documented example) affects the eye retina. Sporadic cases appear at children age in one eye whereas familial cases with inherited mutation in RB1 gene come sooner and are present in both eyes and tumors can develop in other organs as well.
 * A typical example:
 * APC gene – Adenomatosus polyposis coli – important in colon cancer development. People with inherited APC mutation develop Familial adenomatosus polyposis (FAP) syndrome. At a young age, they have hundreds of polyps in their colon and have 100% chance to develop cancer. The gene APC codes for protein, a part of a protein complex, capable of affixing the β-catenin molecule in cytoplasm. Once mutated, cell loses the control of the cell cycle and regulation of the Wnt signaling pathway.
 * TP53 gene – gatekeeper gene, controls the DNA repair status in the nucleus of the cell. If DNA seems to be too damaged and repair insufficient then it leads the cell to apoptosis. This protein is called the “Guardian of the Genome”. Inherited allele leads to Li-Fraumeni syndrome.
 * BRCA 1,2 gene – It is a typical caretaker gene. Protein BRCA1 is a part of a multi-subunit protein complex that participates in transcription, double-strand break repair and recombination. Inherited allele leads to breast and ovarian cancer.