The Basics

This page includes simple definitions that maybe useful when reading this site. More comprehensive explanations can be found elsewhere. If there are other terms you would like to see, drop me a line. Some terms do not have single, universal definition and can be used differently in different contexts!

What is the genome? The term ‘genomeis used to describe our entire genetic information, and is present in each of our cells. The genome is made of DNA which is itself made of 4 building blocks denoted by the letters A, C, G, T. The order and position of the letters determines the function of that part of the genome. The human genome contains over 3 billion letters.

What is a gene? Genes are the parts of the genome that code for proteins, which in turn provide the instructions that make our bodies works. There are about 20,000 genes in the genome. The genes only take up 1/40th of the genome. Genes are the part of the genome that we understand the best.

What is a mutation? A mutation is a change in the DNA code. There are many different types of mutation. For example single letter changes, removal or insertion of letters or rearrangement of letters, such that the normal order is disrupted. Sometimes mutation is reserved for changes that have deleterious effects, for example changes that stop genes working. I tend to use mutation in this way. The term variant can be used to denote a DNA change that is not known to have an effect. I tend to use variant in this way.

How do mutations cause cancer? There are two ways in which gene mutations are important in cancer:
1. Mutations in the DNA of the cancer cells can help them evade normal controls so they grow and spread. These mutations are not present in normal cells and are not hereditary. They are sometimes called ‘somatic’ mutations.

2. Sometimes mutations that are present in every cell in the body make it more likely that a normal cell will turn into a cancer cell. Such mutations are either inherited or can start for the first time at conception. Sometimes they can be passed on to offspring. Such mutations are called ‘germline’ or ‘constitutional’ mutations.

What is a cancer predisposition gene? Genes in which germline mutations increase the risk of cancer are called ‘cancer predisposition genes’. These mutations do not cause cancer (otherwise every cell in the body would be a cancer, because the mutation is present in every cell), but they make it more likely that at least one of the cells in the body will turn into a cancer cell. There are over 100 known cancer predisposition genes, together predisposing to >35 different cancers. We estimate that at least 1 in 100 people have a cancer predisposition gene mutation. The frequency is much higher in cancer patients, for example about 1 in 5 women with ovarian cancer have a cancer predisposition gene mutation

How many cancers are genetic? It depends what one means by ‘genetic’. Somatic mutations are a hallmark of cancer. The great majority of cancers will have some mutations in the cancer cells, and therefore could be considered ‘genetic’. However, most people use ‘genetic’ to mean ‘hereditary’. Somatic mutations are not hereditary. Germline mutations in cancer predisposition genes are often hereditary. Overall about 3% of cancers (~300,000 each year worldwide) develop because of a cancer predisposition gene mutation. This is not evenly distributed between cancers. For example ~40% of some childhood cancers, ~20% of ovarian cancers but only a very small number of lung cancers are due to currently known cancer predisposition gene mutations.

What does sequencing mean? The order of letters in the DNA code is the ‘sequence’. The term sequencing has come to mean the reading of the DNA code, either of selected parts or the whole genome.