Medical Genetics - V. M. Zaporozhan 2005

Basics of Oncogenetics
Targets of Gene Action Involved in Carcinogenesis
Viral Oncogenes

The discovery of viral oncogenes is tied to The Study of the Rous Sarcoma virus. In 1911, the American scientist Rous discovered a virus that induces sarcoma in chickens—the Rous sarcoma virus. In the late 1970s, advances in technology made it possible to study the viral genome. The Rous sarcoma virus belongs to the RNA-containing Retroviruses. Its genome consists of four genes, one of which drives the Transformation of a normal host Cell into a tumor cell. This transforming Gene was isolated and designated as the viral oncogene v-src.

It was soon demonstrated that the artificial Introduction of the v-src gene into the host cell's genetic apparatus transforms it into a tumor cell even in the absence of the virus. This revealed that tumor Viruses induce tumorigenesis not by themselves, but because they introduce an oncogene into The Cell's genetic apparatus. If the oncogene is deleted from the viral genome, the virus loses its ability to cause malignant tumor formation.

The study of other Oncogenic Viruses has led to the isolation of additional viral oncogenes (v-onc, derived from viral oncogenes). They are typically designated by a three-letter abbreviation indicating their origin or the type of tumor they induce. Examples of viral oncogenes are given in Table 8.1.

It is hypothesized that viral oncogenes are modified genes of higher organisms (Proto-oncogenes) that were incorporated into the viral genome at some point in the past. However, direct eukaryotic counterparts have not been found for all viral oncogenes. Viruses do not necessarily carry pre-existing active oncogenes; their action may also stem from the activation of cellular proto-oncogenes or the inactivation of Tumor Suppressors.

Today, A wide variety of oncogenic DNA and RNA viruses have been identified. Human DNA-containing oncogenic viruses include human papillomavirus types 16 and 18 (which can induce cervical, penile, and Skin cancers), Epstein-Barr virus (nasopharyngeal carcinoma, Burkitt lymphoma), hepatitis B virus (hepatocellular carcinoma), and herpesvirus (associated with Kaposi sarcoma). Additionally, one RNA-containing retrovirus has been identified: human T-cell leukemia virus type 1 (HTLV1), which causes T-cell leukemia.

A common and characteristic feature of all virus-associated human tumors is that they develop after a prolonged latent period ranging from 5 to 30 years or more. This indicates that, even in the case of viral oncogenes, the complete transformation of a normal cell into a tumor cell requires multiple genetic events associated with somatic Mutations.