ONCOGENES AND TUMOR SUPPRESSOR GENES

A normal cell becomes cancerous if it has defective proto-oncogenes (oncogenes) and tumor suppressor genes, disrupting the balance between cell division and programmed cell death. These genes differ from each other in origin and function. Human genome studies have shown many evolutionarily young or novel genes with tumor-specific or tumor-predominant expression. Studies prove that the oncogenes and tumor-suppressor genes are among the oldest gene classes in humans and play an essential role in cancer development in our pets.

Proto-oncogenes are genes that, if activated during cell division, give rise to oncogenes which, upon further multiplication, lead to cancer. Activation of proto-oncogenes to oncogenes occurs by different mechanisms like gene insertion or deletion, translocation, gene amplification, and point mutation. For example, researchers show that a protein derived from an oncogene in canine papillomavirus is a cancer in companion animals.

Tumor suppressor genes prevent or suppress cancer formation by altering cell division regulation, leading to uncontrolled cell growth and thus affecting cancer progression. The scientific community regards these genes as the key players in the genesis of cancer. Although many of these cancer genes are known, those with the most significant impact are the RBI and p53 genes. Both are involved in making an RNA copy (called messenger RNA–mRNA) of a gene’s DNA sequence. The mRNA of the RB1 and p53 genes impact regulating events in the cell division cycle.

On the DNA of a cell, there are 2 versions of a gene. Each version, or “allele”, comes from a parent, where one allele is from the mother and one from the father. Additionally, each gene encodes for a specific protein. For the proto-oncogene, each allele must produce a molecule of the protein that starts cell division. If the proto-oncogene allele is mutated, it will lead to oncogene development and the eventual formation of an abnormal protein, causing unregulated cell growth. Mutations usually occur in somatic cells (non-egg and sperm), making them less likely to be inherited.

A tumor suppressor gene codes for a protein that acts as a stop signal for cell division. If both alleles of the tumor suppressor gene are mutated, the resulting altered proteins will not be able to stop cell division properly. Therefore, the cells will continue to divide, leading to the formation of a tumor. Mutations may occur in egg or sperm cells (germline) or somatic cells, making tumor suppressor genes easily passed on to future generations.

Because proto-oncogenes are responsible for starting cell division, when oncogenes form, there is a resulting new protein with a new role. Therefore, proto-oncogenes become oncogenes through a “gain-of-function” mutation and stimulate cell growth and division. Alternatively, because alterations in tumor suppressor genes lead to a protein that stops normal function, the genes are inactivated by “loss-of-function” mutations, and tumor cells are permitted to grow continuously.

To gain a clearer picture of oncogenes and tumor suppressor genes, you can refer to the following table, which highlights their significant differences:
 

Oncogenes	Tumor suppressor genes
A mutated proto-oncogene with a gain-of-function that promotes uncontrolled cell division.	A gene with a loss-of-function mutation that causes unrestrained cell division.
Causes cancer.	Unless mutated, protects cells from becoming cancerous.
Dominant at the cellular level. Mutation in one of the two copies of the proto-oncogene is sufficient to cause cancer.	Recessive at the cellular level. Both copies of the gene must be mutated to cause cancer.
Mutations often occur in somatic cells and are not inherited.	Mutations may occur in somatic cells or germ cells (inherited).

 

Scientists have developed a computational tool called DORGE for predicting the likelihood of genes like oncogenes and tumor suppressor genes to occur. With resources like DORGE, pet cancer science can significantly improve and lead to better outcomes for our furry friends.