Oncogenes

What are oncogenes?

An oncogene is a gene that may cause cancer. It’s a mutated (changed) form of a normal gene, called a proto-oncogene, that manages cell growth. When proto-oncogenes mutate into oncogenes, they cause cells to grow and divide uncontrollably. Eventually, the abnormal cells may form tumors. Think of it this way: Oncogenic means “causing tumor growth.” And this is what oncogenes do.

Understanding how oncogenes drive tumor growth helps healthcare providers develop treatments targeting oncogenes. It helps them treat the cancers that oncogenes cause.

Types of oncogenes

Providers have linked more than 100 different oncogenes to various kinds of cancer. For example, approximately 1in 5 cancers involve various forms of Ras genes. Ras genes make proteins that manage how cells receive signals, grow and die.

Other oncogenes are associated with specific kinds of cancer, including:

• BCR/ABL1 gene in chronic myeloid leukemia and some types of B-cell acute lymphocytic leukemia
• CMYC gene in Burkitt lymphoma
• EGFR and EML4AK genes in adenocarcinoma of the lung
• HER2 gene in breast cancer
• KRAS gene in pancreatic cancer, colon cancer and lung cancer
• NMYC gene in small cell lung cancer and neuroblastoma

How do oncogenes work?

To understand how oncogenes work, you need to know about proto-oncogenes. Proto-oncogenes are normal genes that may mutate and become oncogenes.

Your body contains trillions of cells. Each cell contains different genes that manage different activities. Proto-oncogenes drive the cell cycle, which is the process cells go through before they can divide and make new cells. Proto-oncogenes also control how fast cells grow, when cells divide and when cells die (apoptosis).

When a proto-oncogene mutates and becomes an oncogene, the gene never stops sending signals telling cells to grow and divide. Cells respond by multiplying faster than usual, eventually creating tumors.

What triggers proto-oncogenes to mutate?

Providers aren’t sure why oncogenes form, but many things that cause cancer likely play a role. This includes overexposure to sunlight or cancer-causing substances (carcinogens). Certain viral infections may also play a role.

Instead of being a genetic mutation you inherit, most oncogenes develop during a person’s lifetime.

Proto-oncogenes mutate in different ways:

• Point mutation. Cells copy their DNA (which contains genes) when they’re ready to divide and make new cells. But sometimes, a change, addition or deletion happens in the DNA, causing a proto-oncogene to become an oncogene.
• Gene amplification. Sometimes, a chromosome (the structure that carries DNA) has too many copies of a certain gene.
• Chromosomal rearrangement. Sometimes, a piece of one chromosome breaks off and swaps places with another chromosome. This process, called translocation, can create an oncogene.

Sometimes, oncogenes and mutated tumor suppressor genes work together to cause cancer. Tumor suppressor genes are another class of genes that may cause cancer.

Why are oncogenes important to cancer treatment?

Cancer typically happens when several genes mutate. For example, most cancerous tumors show signs of 30 to 60 different genetic mutations. But oncogenes are powerful. In some cases, a single oncogene may trigger cell growth that leads to cancer.

But there’s a potential upside. It’s easier for healthcare providers to target one genetic mutation than many mutations, making cancer treatment more effective.

For instance, they know chronic myelogenous leukemia (CML) happens when a single type of proto-oncogene mutates and becomes BCR-ABL oncogenes. The oncogene makes abnormal enzymes that let abnormal white blood cells multiply uncontrollably.

Tyrosine kinase inhibitor (TKI) drugs block abnormal BCR-ABL enzymes so the abnormal white blood cells die. This puts CML into remission. Remission means you don’t have signs or symptoms of cancer. Before this treatment, only about 1 in 5 people with CML were alive five years after diagnosis. But now, people are living significantly longer because of drugs designed to target the oncogene.

Is p53 an oncogene?

No, p53 is a tumor suppressor gene. But like an oncogene, it can lead to cancer. Tumor suppressor genes tell cells when to stop making more cells. But if a tumor suppressor gene mutates, it can no longer send the “stop” signal. The cells can multiply out of control and form tumors.