Tumour Suppressor Genes

Abstract

Abstract Tumour suppressor genes are a group of genes whose loss contributes to malignancy. The original hypothesis surrounding tumour suppressor genes defined a ‘two‐hit’ requirement for mutagenesis; however, it is now known that deletion, silencing or downregulation of one or more genes may lead to cancer formation. There is a growing list of putative tumour suppressor genes, and recently several new candidates were added. Research into apoptosis, or programmed cell death, continues to expand. As pathways for which tumour suppressor genes are responsible become clearer, so do potential therapeutics to capitalise on these targets. A summary of the mechanisms by which tumour suppressor genes may act, the mutations which lead to tumourigenesis, and the clinical implications of these phenomena are presented. Key Concepts: Tumour suppressor genes prevent mutagenesis. Perturbation of tumour suppressor gene function may lead to cancer formation. The first tumour suppressor gene identified was the Rb gene, and mutations in the gene lead to the childhood cancer known as retinoblastoma. Although many tumour suppressor genes require two mutations to cause a loss‐of‐function, in some cases, downregulation of a single tumour suppressor gene may lead to cancer. The p53 gene is involved in a complex pathway of cell death and cell arrest, and mutations in p53 or other genes in the pathway can lead to the development of cancer. There are several other modulators of tumour formation, including telomeres, adhesion molecules and microRNA, that may function like tumour suppressor genes. Identification of tumour suppressor genes has lead to the development of anticancer therapeutic agents targeted to specific pathways that take advantage of this knowledge.