Understanding how genes can cause cancer

Acquired mutations arise from damage to DNA during a person’s life, such as from ageing, viruses, UV radiation and certain chemicals.

In 1911, an American research scientist Peyton Rous, whilst working at the Rockefeller Institute in New York, found that by transplanting bits of a malignant tumour from one hen into other hens, they too produced malignant tumours.

Rous later took a sample of the tumour and passed it through a filter.

Intact cells and any bacteria were trapped by the filter but to his surprise after injecting the fluid that passed through the filter into a healthy hen, it acquired a malignant tumour.

Something in the ‘‘filterable agent’’, as Rous called it, was causing the cancer.

The filterable agent was a virus – later named Rous Sarcoma Virus (RSV), the first tumourcausing virus to be discovered.

The scientific world was slow to appreciate the significance of Rous’s discovery – he was not awarded a Nobel Prize until 50 years after he first published the results.

Decades later scientists discovered how the RSV virus worked.

A brief background follows.

All forms of life have nucleic acids of which there are two types, deoxyribose nucleic acid (DNA) and ribonucleic acid (RNA).

DNA, the information store in most forms of life, is a very long double-stranded molecule.

There is a DNA molecule in each of the estimated 40 trillion cells in the human body.

RNA is more often found as a single-stranded molecule and fulfils multiple roles in the cell such as conveying messages, coding, decoding and regulating the production of proteins.

An important difference in the RSV virus is that information is stored in RNA not DNA.

A section of DNA or RNA is called a gene, there are about 20,000 genes in a single molecule of human DNA.

Genes control how the cell functions and there are three aspects of cell function relevant to cancer; how quickly the cell grows, how often it divides and how long it lives.

All cancers begin when one or more genes mutate.

A mutated gene can alter the function of the cell, for example it can make it multiply uncontrollably and produce a malignant tumour.

There are two basic types of gene mutations, acquired mutations and germline mutations.

Acquired mutations arise from damage to DNA during a person’s life, such as from ageing, viruses, UV radiation and certain chemicals.

Germline mutations occur in sperm or egg cells and can be passed from parent to child.

Cancers caused in this way are called inherited cancers and according to the American Society of Clinical Oncology, account for about 10 per cent of all cancers.

In 1976 Michael Bishop and Harold Varmus of the University of California used Rous’s RSV virus to demonstrate how malignant tumours are formed from normal cell genes.

A gene that has potential to cause cancer is called an oncogene. Bishop and Varmus found that oncogenes are present in specific parts of some viruses.

An important discovery, however, was that the oncogene was not actually a section of true viral gene but a normal cell gene, a proto-oncogene, that had been picked up by the virus when it hijacked the hen host’s cell machinery.

After further investigation they discovered that proto-oncogenes produce an enzyme that stimulates cell growth and cell division.

There are many types of proto-oncogene found in human DNA, but if these mutate they can trigger cancer.

Today three categories of these genes have been identified.

First, the oncogenes that Bishop and Varmus investigated.

Secondly, there are tumour suppressor genes which monitor, repair and control cell growth – if these mutate then the cells grow uncontrollably and may lead to a malignant tumour.

Thirdly, there are DNA repair genes – these fix any mistakes made in copying DNA, but if these repair-genes mutate the result can be cancer.

‘‘Cancer’’ is defined as a group of diseases linked to abnormal cell growth which can spread to other parts of the body.

Many cancers are linked with multiple genes which is one of the reasons cures for cancer have been so elusive.

Challenges remain but progress since Rous’s work in 1911 has been remarkable and many types of cancers are much better understood.

Future work will be directed at how to predict a person’s risk of cancer, diagnosing and coming up with more effective treatments.