American Association for Cancer Research

Basic Biology and Cancer


Somatic and Germ-Line Mutations

The vast majority of the mutations that contribute to cancer formation are somatic mutations. This means that they occur in the DNA of a somatic cell, which is a cell that has a full set of chromosomes but is not used in the creation of the next generation of offspring.

If I wanted to take cells from you to make another person, I couldn’t just take any cells. I would need germ cells. In a female, this would be the egg cells; in a male, this would be the sperm cells. A brain cell wouldn’t work, because it's a somatic cell; it’s not a germ cell. The germ cells—the egg cells and the sperm cells—differ from somatic cells. Somatic cells have two sets of chromosomes; germ cells have only one. The germ cells are the cells that come together to make an embryo. Once the embryo is formed, it begins to produce the somatic cells, which will start developing into fingers, or the brain, or the eyes, or other parts of the body. Your children will not inherit any of your somatic cells. Your somatic cells stay with you; they grow and divide to create new cells for your body. If a somatic cell has a mutation, it will pass that mutation onto its two daughter cells. But that mutation will not be passed on to any children you might have. That’s because the only genes that you pass on are the genes that are in your germ cells—in your sperm or your eggs. So, while somatic mutations are genetic mutations, they are not passed on to the next generation of offspring.

As I said before, cancer is a genetic disease in that it alters the genetic code at the cellular level. But that doesn’t mean necessarily that it's a hereditary disease. At one of the first talks I gave on cancer genetics, someone said, “Not all cancers are hereditary. So why is cancer genetic?” And this is something that is important to understand. We are talking about the genes of somatic cells that are not passed on to offspring. Cancer genetics, therefore, is not necessarily the study of hereditary cancer but rather the study of genetic mutations that contribute to the genesis of cancer.

A germ-line mutation is different from a somatic mutation. A germ-line mutation is an alteration of the DNA of one of the germ cells—the sperm cells and the egg cells. If my sperm has a genetic mutation, then any embryo that develops from that sperm will carry that genetic mutation. It will be in the first embryonic cell—remember, we all start from one cell—and it will then go on to be in every single cell in my offspring’s body. We call that a germ-line mutation because it started in one of the germ cells.

A normal sperm cell has normal copies of half the chromosomes. But let’s say my partner has a mutation in her half of the chromosomes in the egg. When my sperm and her egg come together, they will make an embryo with a full set of chromosomes. That’s the embryonic stem cell, and from that one cell will come all of the somatic cells that will form into our offspring. And because my partner had a mutation in her germ cells, every one of the cells in our offspring’s body is going to have a germ-line mutation in her or his DNA. And every child that my child has will also inherit this mutation, because this mutation is in my child’s germ cells.

Germ-line mutations can cause an increased risk of developing cancer, but they are rarely directly involved in the development of cancer. If I pass on a germ-line mutation, that doesn’t mean that my child is going to be born with cancer. But it does mean that she or he will be born with one mutated tumor-suppressor gene. Remember, as we discussed earlier, both genes must become mutated for the tumor-suppressor gene to stop working. So someone who is born with one that is already mutated has got a head start on developing cancer because one of the genes is already messed up. So if the other gene gets hit, or mutated, they are going to get cancer. Some people will never get that hit, never develop that mutation, and never develop cancer. So having the mutation doesn’t mean you will get cancer, but you are at increased risk.

To close, we have discussed and defined cancer, the causes of cancer, the six hallmarks of cancer, the cell cycle, oncogenes, dominant and recessive tumor suppressive genes, and somatic mutations and germ-line mutations. Thank you very much.