X-ray of normal and transgenic mice

Types of gene involved in cancer

8/6/00. By Giles Newton

Mutations in several different types of genes are involved in cancer. Some of these genes control growth, or stop excessive growth, while others control a cell's blood supply or its position in the body.

Proto-oncogenes: genes that encourage the growth of a cell

A mutation can turn one of these genes into a cancerous oncogene that drives excessive cell division. Oncogenes can encode signalling molecules such as growth factors, or components of the signalling cascades that regulate the mediate the cellular responses to such signalling molecules.

Tumour suppressor genes: genes that stop excessive growth of the cell

If a cell starts to divide excessively, its neighbours send inhibiting factors to quieten it down. Such factors either act directly or trigger inhibitory factors in the rogue cell. A key phase in the development of a cancer cell comes when it develops one or more mutations - in so-called tumour suppressor genes - which enable it to ignore its neighbours. Mutations can knock out a cell-surface receptor for inhibiting factors, or a critical component of the cascades inside the cell that receive and process the signal. Other mutations can disable proteins such as p53, which trigger the cell to commit suicide (undergo apoptosis) if its DNA becomes damaged, or its signalling cascades go out of control.

Angiogenic genes: genes that control a cell's blood supply

If a cell becomes cancerous and begins dividing rapidly, the daughter cells pile up in a mass. But as the mass expands, it needs to increase its supply of oxygen and nutrients; without such an increase, it will reach a steady-state size - about that of a pea - where the number of new cells is matched by dying cells. Such small carcinomas can stay in the body for months or years without gaining size, but there is always the risk that one of the cancer cells will acquire a further mutation in a gene that regulates angiogenesis - the production of factors that promote the growth of new blood vessels. When this occurs, hundreds of new capillaries converge on the tumour, which gains the supplies it needs to grow in size.

Metastasis genes: controlling the spread of cancer

Most cells are restricted to a particular place within a tissue, with their neighbours helping to define where that position should be. If a cell becomes detached from the tissue it usually stops proliferating and dies. But a cancer cell can acquire mutations in certain genes that allow it to spread to other parts of the body.

Although in theory three mutations alone could lead to cancer, it is thought that most common adult cancers are caused by at least five mutations, and probably more. About 100 cancer genes have been found, but many more are thought to be undiscovered. Most of the 100 known genes have been found in the relatively rare leukaemias and lymphomas, which account for less than 10 per cent of all human cancer; for the common adult epithelial cancers of the breast, colon, prostate, lung and ovary, which account for 80 per cent of the cancer burden, only about 30 genes are known.

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