Oncogenes, Tumor Suppressor Genes and DNA Repair Genes

Overview

The body is made of trillions of cells that divide to grow and to replace cells that die. That division has to be controlled so cells do not overgrow and crowd out their neighbors. Genes on our chromosomes do the controlling, and changes in them can lead to cancer. Three kinds of genes play the main roles — oncogenes, tumor suppressor genes and DNA repair genes — and cancer often involves changes in more than one kind.

Oncogenes

Proto-oncogenes help control normal cell growth and division. When a proto-oncogene changes or becomes too active, it becomes an oncogene, and the cell can grow out of control and survive when it should die. Two common examples:

• HER2 makes a protein that drives cancer growth. It is found in some breast and ovarian cancer cells. HER2-positive breast cancer usually has too many copies of the HER2 gene.
• The RAS family makes proteins that help cells communicate, grow normally and die on time. Changes in these genes can turn healthy cells into cancer cells.

An oncogene can be created or switched on by a gene change (inherited or acquired); by a chromosome rearrangement (translocation), where DNA is rearranged during division and an "on" switch lands next to a proto-oncogene; by an epigenetic change, where chemical groups attached to DNA or RNA turn the gene on; or by gene duplication, where extra copies of a gene make too much of a protein. A few family cancer syndromes come from an inherited oncogene, but most oncogenes arise during a person's life.

Tumor Suppressor Genes

Tumor suppressor genes slow cell division or tell damaged cells to die (apoptosis, or programmed cell death). They protect against cancer, and when they stop working, cells can grow out of control. Some inherited changes in these genes run in families and raise cancer risk, but most changes happen during life. For example, the TP53 gene makes the p53 protein, which helps control cell division. Rare inherited TP53 changes cause Li-Fraumeni syndrome, which raises the risk of several cancers in a family. TP53 changes are more often found only in the cancer cells of people without an inherited syndrome, and those cannot be passed to children.

DNA Repair Genes

Every time a cell divides it copies all its DNA, and mistakes can happen. DNA repair genes fix them, or make the cell die if a mistake cannot be fixed. When a repair gene fails, mistakes build up and can affect other genes, letting cells grow out of control. These changes can be inherited or acquired. For example, BRCA1 and BRCA2 help repair DNA. People who inherit certain changes in either gene have a higher risk of some cancers, especially breast and ovarian cancer in women. These changes can also occur in people who did not inherit them.

Questions to Ask Your Doctor

• Has my tumor been tested for changes in genes such as HER2, RAS, TP53 or BRCA?
• Are any gene changes found in my cancer inherited, or only in the cancer cells?
• Does my family history suggest a syndrome such as Li-Fraumeni or hereditary BRCA changes?
• Are there treatments that target the gene changes found in my cancer?
• Should my relatives be tested if an inherited change is found?

Source: https://www.cancer.org/cancer/understanding-cancer/genes-and-cancer/oncogenes-tumor-suppressor-genes.html