Oncogenes and Tumor Suppressor Genes

Two of the main types of genes that play a role in cancer are oncogenes and tumour suppressor genes.

Oncogenes

Proto-oncogenes are genes that normally help cells grow. When a proto-oncogene mutates (changes) or there are too many copies of it, it becomes a “bad” gene that can turn on permanently when it’s 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.

It can be helpful to think of a cell as a car. For it to work properly, there must be ways to control how fast it goes. A proto-oncogene normally works much like an accelerator. It helps the cell to grow and divide. An oncogene could be compared to an accelerator that is stuck, causing the cell to divide uncontrollably.

Some cancer syndromes are caused by inherited mutations of proto-oncogenes that cause the oncogene to turn on (activate). But most cancer-causing mutations involving oncogenes are acquired, not inherited. They generally activate oncogenes by:

  • Chromosomal rearrangements: Chromosome changes that place one gene next to another, allowing one gene to turn on the other
  • Gene duplication – having extra copies of a gene, can lead to making too much of a certain protein

Tumour suppressor genes

Tumour suppressor genes are normal genes that slow cell division, repair DNA errors, or tell cells when to die (a process known as apoptosis, or programmed cell death). When tumour suppressor genes don’t work properly, cells can grow out of control, which can lead to cancer.

A Genprice Tumor Suppressor Gene is like the brake pedal on a car. It normally prevents the cell from dividing too quickly, much like a brake prevents a car from going too fast. When something goes wrong with the gene, such as a mutation, cell division can go out of control. An important difference between oncogenes and tumour suppressor genes is that oncogenes result from the activation (turned on) of proto-oncogenes, but tumour suppressor genes cause cancer when they are inactivated (turned off).

Inherited abnormalities of tumour suppressor genes have been found in some familial cancer syndromes. They cause certain types of cancer to run in families. But most tumour suppressor gene mutations are acquired, not inherited. For example, abnormalities in the TP53 gene (which codes for the p53 protein) have been found in more than half of human cancers. Acquired mutations of this gene appear in a wide range of cancers.

Addition and Deletion Mutations

Description

Mistakes occasionally do occur spontaneously during DNA replication, causing changes in the sequence of nucleotides. Such changes, or mutations, also can arise from radiation that causes damage to the nucleotide chain or from chemical poisons, such as those in cigarette smoke, that lead to errors during the DNA-copying process. Mutations come in various forms: a simple swap of one nucleotide for another; the deletion, insertion, or inversion of one to millions of nucleotides in the DNA of one chromosome; and translocation of a stretch of DNA from one chromosome to another.

Mutated genes that encode altered proteins or that cannot be controlled properly cause numerous inherited diseases. For example, sickle cell disease is attributable to a single nucleotide substitution in the haemoglobin gene, which encodes the protein that carries oxygen in red blood cells. The single amino acid change caused by the sickle cell mutation reduces the ability of red blood cells to carry oxygen from the lungs to the tissues. Recent advances in detecting disease-causing mutations and in understanding how they affect cell functions offer exciting possibilities for reducing their often devastating effects.

What types of genetic variants are possible?

The DNA sequence of a gene can be altered in various ways. Genetic variants (also known as Addition and Deletion Mutations) can have a variety of health effects, depending on where they occur and whether they alter the function of essential proteins. Variant types include the following:

1. Substitution

This type of variant replaces one DNA building block (nucleotide) with another. Substitutional variants can be further classified by the effect they have on protein production from the altered gene.

  • Missense: A missense variant is a type of substitution in which the nucleotide change results in the replacement of one protein building block (amino acid) with another in the protein made from the gene. The amino acid change can alter the function of the protein.
  • Nonsense: A nonsense variant is another type of substitution. However, instead of causing an amino acid change, the altered DNA sequence results in a stop signal that prematurely tells the cell to stop building a protein. This type of variant results in a shortened protein that can malfunction, not work, or break down.

2. Insertion

An insertion changes the DNA sequence by adding one or more nucleotides to the gene. As a result, the protein made from the gene may not work properly.

3. Suppression

A deletion changes the DNA sequence by removing at least one nucleotide in a gene. Small deletions remove one or a few nucleotides within a gene, while larger deletions can remove an entire gene or several neighbouring genes. The removed DNA can alter the function of the affected protein(s).

4. Delete-Insert

This variant occurs when a deletion and an insertion occur at the same time at the same location in the gene. In a deletion-insertion variant, at least one nucleotide is removed and at least one nucleotide is inserted. However, the change must be complex enough to differ from a simple substitution. The resulting protein may not work properly. An insertion-deletion variant (dealings) may also be known as an insertion-deletion variant (indel).

5. Duplication

Duplication occurs when a stretch of one or more nucleotides in a gene is copied and repeated along with the original DNA sequence. This type of variant can alter the function of the protein made from the gene.

6. Investment

An inversion changes more than one nucleotide in a gene by replacing the original sequence with the same sequence in reverse order.

7. Frame change

A reading frame consists of groups of three nucleotides that each code for an amino acid. A frameshift variant occurs when there is an addition or loss of nucleotides that changes the grouping and changes the code for all subsequent amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can be frameshift variants.

8. Repeat expansion

Some regions of DNA contain short sequences of nucleotides that are repeated several times in a row. For example, a trinucleotide repeat is made up of sequences of three nucleotides and a tetranucleotide repeat is made up of sequences of four nucleotides. A repeat expansion is a variant that increases the number of times the short DNA sequence is repeated. This type of variant can cause the resulting protein to not work properly.

Genetic Engineering

Genetics

Genetics has come a long way since Gregor Mendel introduced his work on peas. Genetic techniques are now used throughout biology, and genetics has an impact on many aspects of life. Gentaur Genetics research frequently uses model systems, which consist of a well-characterized subset of organisms. Many of the Biotechnology Explorer™ modules also use model organisms, for example, the C. elegans Behavioral Kit and the pGLO™ Bacterial Transformation Kit. With these kits, students can gain experiences similar to those found in working research labs.

Genetic Engineering Applications

Genetic engineering means the manipulation of organisms to make useful products and has wide applications.

  • New DNA can be inserted into the host genome by first isolating and copying the genetic material of interest, using molecular cloning methods to generate a DNA sequence; or by synthesizing the DNA and then inserting this construct into the host organism. Genes can be removed, or “knocked out,” using a nuclease.
  • Gene targeting is a different technique that uses homologous recombination to change an endogenous gene and can be used to delete a gene, remove exons, add a gene, or introduce point mutations. Genetic engineering has applications in medicine, research, industry, and agriculture and can be used in a wide range of plants, animals, and microorganisms.
  • Genetic engineering has produced a variety of drugs and hormones for medical use. For example, one of its earliest uses in pharmaceuticals was the splicing of genes to make large amounts of insulin from cells of E. coli bacteria. Interferon, which is used to eliminate certain viruses and kill cancer cells, is also a product of genetic engineering, as are tissue plasminogen activator and urokinase, which are used to dissolve blood clots.
  • Another byproduct is a type of human growth hormone; it is used to treat dwarfism and is produced through genetically modified bacteria and yeasts. The evolving field of gene therapy involves the manipulation of human genes to treat or cure genetic diseases and disorders. Modified plasmids or viruses are often the messengers that deliver genetic material to the cells of the body, resulting in the production of substances that should correct the disease. Sometimes cells are genetically modified within the body; other times scientists modify them in the laboratory and return them to the patient’s body.
  • Since the 1990s, gene therapy has been used in clinical trials to treat diseases and conditions such as AIDS, cystic fibrosis, cancer, and high cholesterol. The drawbacks of gene therapy are that sometimes the person’s immune system destroys cells that have been genetically altered, and also that it is difficult to get the genetic material into enough cells to have the desired effect.

Recombinant DNA Technology Biochemicals

Many practical applications of recombinant DNA are found in human and veterinary medicine, agriculture, and bioengineering. Recombinant DNA technology is the latest biochemical assay to emerge to meet the need for specific DNA segments. In this process, the surrounding DNA of an existing cell is cut into the desired number of segments so that it can be copied millions of times.

Recombinant DNA technology modifies microbial cells to produce foreign proteins, and its success depends solely on the precise reading of equivalent genes created with the help of bacterial cell machinery. This process has been responsible for driving many advances related to modern molecular biology. The last two decades of studies of cloned DNA sequences have revealed detailed knowledge about gene structure as well as its organization.

It has provided clues about the regulatory pathways with the help of which cells control gene expression in countless cell types, especially in those organisms that have a body plan with a basic structure of vertebrae. Recombinant DNA technology, in addition to being an important scientific research tool, has also played a vital role in the diagnosis and treatment of various diseases, especially those belonging to genetic disorders.

Some of the recent advances made possible by recombinant DNA technology are:

1. Protein isolation in large quantities: Many recombinant products are now available, including follicle-stimulating hormone (FSH), Follistim AQ vial, growth hormone, insulin, and some other proteins.

2. Enable identification of mutations: Thanks to this technology, people can easily test for the presence of mutated proteins that can lead to breast cancer, neurofibromatosis, and retinoblastoma.

3. Diagnosis of hereditary disease carriers: Tests are now available to determine if a person is a carrier of the gene for cystic fibrosis, Tay-Sachs diseases, Huntington’s disease, or Duchenne muscular dystrophy.

4. Transfer of genes from one organism to another: Advanced gene therapy can benefit people with cystic fibrosis, vascular disease, rheumatoid arthritis, and specific types of cancer.