discovery

Oncogenes and tumor suppressor genes

Key Points:

  • Not all genes are capable of promoting cancer.  Those that can are called proto oncogenes.
  • Once proto oncogenes are damaged (mutated) they become oncogenes and promote cancer.
  • Most proto oncogenes are involved in the processes of cell growth, survival and proliferation.
  • There are many different types of proto oncogene, but they are not all equal.  Some play a much more central role in cancer development than others.
  • Oncogenes are only half the story – tumor suppressor genes help by controlling cell growth, repairing DNA and promoting cell suicide when repair fails.
  • You can think of oncogenes as the accelerator on a car; tumor suppressor genes are the brakes.  When both fail, cancer can take hold.

Created by 10 cancer experts, our video series is a must for patients / families

Learn what you can do to help

What are oncogenes?

At their most basic, oncogenes are genes that promote cell growth and therefore cancer growth.  “Onkos” is the Greek word for “tumor” or “mass”, and thus oncogenes are genes that promote such.

Not all genes are, however, capable of promoting or producing cancer.  It’s not any gene that can become an oncogene.  The genes that can mutate into oncogenes are typically involved in the process of cell growth, survival and proliferation.  These genes that are able to become oncogenes, and cause cancer, are called proto oncogenes.

What are some examples of oncogenes?

Oncogenes are often given three letter names RAS, WNT, MYC, and there are many of them.  That said, evidence indicates that a relatively small number of 15 or so are involved in a large number of cancers, indicating that, for a great many patients, it is a handful of genes that are playing a key role.1   This is interesting and has particular ramifications for treatment – it means that treatments targeting these key genes / pathways will be potentially effective in many different cancer types.

Cancer doctors and researchers think in terms of pathways and we encourage patient and their supporters to do the same.  Many of the same pathways underpin different cancer types.  In our Video Series, we explain in easy to understand terms a six-pathway model for understanding cancer.

While many oncogenes are normally implicated in cancer, some cancers are inextricably linked to a small number of genes.  For example, a rare type of cancer called Burkitt’s Lymphoma is closely linked to the MYC gene.

In what ways can proto oncogenes be converted to oncogenes?

It’s important to understand that proto oncogenes are not in and of themselves bad.  What then is the difference / relationship between oncogenes and proto oncongenes? To the contrary, they are fundamental to life as they regulate cell growth.  Cells, and thus humans, cannot grow and renew themselves without these genes.  Without them life would not exist.

It is only when these genes become damaged that good become bad,2 that proto oncogenes become oncogenes and contribute to cancer.  The precise mechanisms involved in this transition are beyond the scope of this article but the key point is that changes occur primarily due to two factors – copying errors (when cells divide) and environmental damage from carcinogens, such as those found in some foods, tobacco smoke and ultraviolet light.

These changes lead to oncogenes being “over expressed”,3 which means they cause cells to grow when they shouldn’t, ultimately leading to cancer (provided the protection mechanisms fail – discussed below).

A simple yet helpful analogy here is that of a car.  Oncogenes are the equivalent of having an accelerator that is stuck to the floor.

What are tumor suppressor genes and what do they do?

Tumor suppressor genes are the opposite to proto oncogenes – these are genes that control cell growth, repair DNA where possible, and promote cell suicide when repair is not possible.  In our car analogy, these are the brakes.

As explained in our Video Series, human DNA is easily damaged – these changes (mutations) can lead to survival advantages (think Darwin), but can also lead to cancer.  In other words, they are responsible for elevating humans beyond middle-of-the-food-chain apes, but equally responsible for millions of cancer deaths each year.

BRCA4 Proto Oncogenes

The BRCA proto oncogenes provide an interesting example of how certain proto oncogenes influence the likelihood of developing cancer.  Most people will have heard of the BRCA1 and 2 genes.  Those with mutations to these proto oncogenes are far more likely to develop cancer.  There is, of course, no guarantee that mutations to these genes will lead to cancer, but the probability of developing certain cancers is greatly increased.  In fact, as shown in the table below, the figures are startling, indicating just how important a role these proto oncogenes have in cancer development, and not just in breast cancer:

Type of Cancer

Population Risk

BRCA Risk

Breast cancer – by age 40

    0.5%

  10-20%

Breast cancer – by age 50

    2%

  33-55%

Breast cancer – by age 70

    8%

  40-85%

Male breast cancer – by age 70

    < 1%

    7%

Ovarian cancer – by age 70

    < 2%

  27-44%

Prostate cancer

    7-15%

  40%

Pancreatic cancer

    < 1%

  2-4%

 

Summary

Like a car our cells are normally carefully regulated with a balance between ‘accelerator’ genes and ‘brake’ genes. If either of these groups of proto oncogenes or tumor suppressor genes become damaged (mutated) then this fine balance is disturbed leading to unchecked cell growth and the potential to develop cancer. It is important to note that not all oncogenes and tumour suppressor genes are equally important. It is also important to note that not all mutations are equal and there is a hierarchy of mutations.  This will be covered in future lectures.  At this stage it is useful to know that mutations in these genes may cause cancer.

Thomas RK et al, High-throughput Oncogene Mutation Profiling in Human Cancer, Nature Genetics 39, 347-351 (2007)
Some oncogenes are heritable, meaning they can be passed down to one’s children and thus do not per se result from copying errors or environmental damage.
Over and under expression of genes is the topic of epigenetics. Genes are not simply on or off, but rather it is a matter of degree. Over-expressed oncogenes do too much, and under-expressed tumor suppressor genes too little. We discuss this in our video series.
BRCA stands for BReast Cancer though the name is something of a misnomer given that that BRCA genes play important roles in multiple cancer types.

Curve.life latest

No spam. 100% help.

wave

Explore sections

Stay in the know

No spam. 100% help.