2020–2021 BCSC Basic and Clinical Science Course™
2 Fundamentals and Principles of Ophthalmology
Part III: Genetics
Chapter 5: Molecular Genetics
Mutations and Disease
Cancer can result from any of a number of genetic mechanisms, including the activation of oncogenes and the loss of tumor suppressor genes. The product of proto-oncogenes is often involved in signal transduction of external messages to the intracellular machinery that governs normal cell growth and differentiation. As such, the DNA sequences of proto-oncogenes are highly conserved in nature between such different organisms as humans and yeast. Proto-oncogenes can be activated to oncogenes by loss or disruption of normal gene regulation.
Oncogenes were first detected in retroviruses, which had acquired them from their host in order to take control of cell growth. These oncogenes are often identified by names that refer to the viral source, as for example, ras (rat sarcoma virus). They are known to be activated not only in virus-induced malignancies but in common nonviral cancers in humans. Oncogenes behave the same way that autosomal dominant traits behave, and only 1 mutant allele is needed for tumor formation, presumably by a dominant-negative effect on regulation of signal transduction.
Tumor suppressor genes
Tumor suppressor genes, also called antioncogenes, are genes that must be present in 1 functional copy to prevent uncontrolled cell proliferation. Although some may represent genes whose products participate in checkpoints for the cell cycle, a characteristic of tumor suppressor genes is the diversity of their normal functions. Examples of tumor suppressor genes include the genes for retinoblastoma, Wilms tumor, neurofibromatosis types 1 and 2, tuberous sclerosis, ataxia-telangiectasia, and von Hippel–Lindau disease. All of these examples (except ataxia-telangiectasia) behave as autosomal dominant traits, but the mechanism of tumor formation for tumor suppressor genes is very different from that for oncogenes. If 1 allele is already defective because of a hereditary mutation, the other allele must also be lost for tumor formation to occur (also known as the 2-hit hypothesis). This loss of the second allele is termed loss of heterozygosity, and it can occur from a second mutation, gene deletion, chromosomal loss, or mitotic recombination.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.