When a proto-oncogene mutates (changes) or there are too many copies of it, it becomes a “bad” gene that can become permanently turned on or activated when it is not supposed to be. When this happens, the cell grows out of control, which can lead to cancer. This bad gene is called an oncogene.

Croce, MD. The first oncogenes were discovered through the study of retroviruses, RNA tumor viruses whose genomes are reverse-transcribed into DNA in infected animal cells. During the course of infection, retroviral DNA is inserted into the chromosomes of host cells.

Later on, the term “oncogene” was rediscovered in 1969 by National Cancer Institute scientists George Todaro and Robert Huebner. The first confirmed oncogene was discovered in 1970 and was termed SRC (pronounced “sarc” as it is short for sarcoma). SRC was first discovered as an oncogene in a chicken retrovirus.

Dr. Weinberg, a founding member of the Institute for Biomedical Research and a professor at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts, is credited with discovering the first human oncogene — the Ras oncogene — which causes normal cells to form tumors.

Everyone has proto-oncogenes in their body. In fact, proto-oncogenes are necessary for our survival. Proto-oncogenes only cause cancer when a mutation occurs in the gene that results in the gene being permanently turned on. This is called a gain-of-function mutation.

Some proto-oncogenes also negatively regulate cell differentiation. Proto-oncogene activities are typically turned off once the developmental processes they regulate are completed. However, if proto-oncogene activity remains high, or if proto-oncogenes are inappropriately reactivated later in life, cancer may occur.

Proto-oncogenes have many functions in a cell but they often code for proteins that stimulate cell division, prevent cell differentiation or regulate programmed cell death (apoptosis). These are all essential processes required for normal growth, development and the maintenance of healthy organs and tissues.

Oncogenes may activate or increase growth factor receptors on the surface of cells (to which growth factors bind). One example includes the HER2 oncogene that results in a significantly increased number of HER2 proteins on the surface of breast cancer cells.

The p53 proto-oncogene can act as a suppressor of transformation. Cell 57, 1083–1093 (1989).

Proto-oncogenes are normal cellular genes that regulate cell growth and differentiation. They often encode products such as growth factors and their receptors, cell cycle regulators, DNA-binding proteins, transcription factors, protein kinases involved in signal transduction, and others.

EGFR and KRAS are reported to be the most frequently altered driver genes, while TP53 is reported to be the most frequently altered tumor suppressor gene in lung adenocarcinoma (Cancer Genome Atlas Research Network 2014; Campbell et al. 2016).

When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally.

Numerous proto-oncogenes other than the ras genes have been shown to be activated in human tumors and to a lesser extent in rodent tumors. Mechanisms that induce aberrant expression of proto-oncogenes are gene amplification and chromosomal translocation or gene rearrangement.

The activation of oncogenes involves genetic changes to cellular protooncogenes. The consequence of these genetic alterations is to confer a growth advantage to the cell. Three genetic mechanisms activate oncogenes in human neoplasms: (1) mutation, (2) gene amplification, and (3) chromosome rearrangements.

HIV-associated cancers include Kaposi sarcoma, non-Hodgkin’s and Hodgkin’s lymphoma, cervical cancer, and cancers of the anus, liver, mouth and throat and lung. There is no vaccine against HIV.

Definition. Viral oncogenesis can be defined as the feature of tumor viruses that induces benign or malignant proliferation of infected cells.

In cells that are non-permissive for replication, viral DNA is usually, but not always, integrated into the cell chromosomes at random sites. Only part of the viral genome is expressed. These are the early control functions of the virus. Viral structural proteins are not made, and no progeny virus is released.

Reverse transcriptases have been identified in many organisms, including viruses, bacteria, animals, and plants. In these organisms, the general role of reverse transcriptase is to convert RNA sequences to cDNA sequences that are capable of inserting into different areas of the genome.