Cancer mutations are a harmful change in DNA that causes a loss of control over cell division. As a result of such damage to the genetic material, cells over-multiply and do not differentiate. They also lose the ability to die as planned. Due to this damage, tissues made of mutant cells grow excessively - this is how cancerous tumors form.
Cancer mutationresults in the loss of mechanisms that block the excessive multiplication of cells. The process of planned cell death, i.e. apoptosis, is also damaged. It should be remembered that not every DNA mutation is a cancer mutation. For a cancer-causing damage to occur, the change must be in the genes that control the cell cycle.
What is the cell cycle?
The cell cycle is a series of processes that lead to cell division. Basically, it can be divided into interphase and division. The interphase serves the growth, synthesis of DNA and the accumulation of substances by the cell. The correct division of a somatic cell, i.e. a cell that builds the body, leads to the formation of two genetically identical cells.
The cycle is controlled by special proteins belonging to the groups of cyclins and kinases. These substances are responsible for communicating the transition to the next phase of the cycle and the start of division. This message may come from the nucleus or from outside, from other tissues in the body.
In the body, most cells are in the G0 mode, which is the resting phase. The division cycle occurs when they receive the appropriate stimulus signal.
How do mutations affect the course of the cell cycle?
If the genes that contain the information needed to synthesize proteins that control the cell cycle are damaged, the cell can divide uncontrollably. This change is called a cancer mutation. As a consequence, the cell is insensitive to signals calling to stop dividing.
Genes responsible for the control of the cell cycle, undergoing mutations, are divided into proto-oncogenes and anti-oncogens.
What are anti-oncogenes?
Antitoncogenesare genes responsible for inhibiting cell division. Another name for them issuppressor genes . This category includes betweenwith others:
- TP53 gene - "guardian of the genome", takes part in the initiation of programmed death of damaged cells. A mutation of this gene is present in 50% of neoplastic lesions
- RB1 - retinal cancer is often associated with damage to this gene
- BRCA1- mutations of this gene can cause breast cancer
- BRCA2 - breast and ovarian cancer may be associated with a mutation of this gene
- APC gene - mutation may cause colon cancer
Proteins encoded by these genes protect against the development of cancer. Ant oncogenes are also involved in DNA repair and control of the development of the nervous system. They control the progression of the cell through the stages of the cycle.
If the DNA is damaged, the proteins encoded by the anti-oncogenes block the transition to the next phase of the division process. This makes them the guardian genes that guard the DNA stability of the body's cells.
If there is a mutation, i.e. a change in the information contained in anti-oncogenes, cell division is not inhibited. As a result, cells with damaged DNA undergo further division. This means uncontrolled multiplication despite its defectiveness. This is a pathway to the formation of neoplastic changes.
What are proto-oncogenes?
Protooncogenis a gene found in a he althy cell that, through a mutation, can turn into a cancer gene. We call this damaged gene an oncogene. This group includes the following genes:
- SIS
- HST
- RET
- erb A
- N-myc
- Fos
- Abl
- H-RAS
Protoncogenes have numerous functions in a he althy cell. This group includes genes needed for the synthesis of growth factor, receptor and regulatory proteins. Their role is to initiate and control cell division. They are also involved in the process of apoptosis.
The conversion of a proto-oncogene into an oncogene is often associated with a chromosomal mutation. This means, for example, the transfer of a fragment of one chromosome to another or the duplication of a fragment of the content contained therein. An example is the Philadelphia chromosome, which is found in 90% of patients with chronic myeloid leukemia.
The process of transforming a proto-oncogene into an oncogene is called oncogenesis. Antitoncogenes are genes that inhibit this process.
What factors can trigger oncogenesis?
Oncogenesis can be caused by a chromosomal or point mutation, i.e. one that affects a single gene. Such a change may also arise as a result of incorporating the DNA of an oncogenic virus into the cell.
The factors that trigger oncogenesis are divided into chemical, physical and biological.
- Chemical agents inducing oncogenesis
Chemical agents are substances of various kinds that have mutagenic properties. These substances are known as carcinogens. They are divided into two groups: initiators and promoters of carcinogenesis. Promoters include endogenous substances that stimulate the development of neoplastic changes, such as estrogens or cytokines.
Initiators are substances that cause mutations in DNA that lead to the formation of a neoplastic lesion. Examples of substances are:
- arsenic
- asbestos
- benzene
- nickel
- alcohol
- alkylating drugs
- aflatoxin - a toxic substance produced by mold
- products resulting from the combustion of tobacco
- dioxins
- radicals
- Physical carcinogens
This category of agents includes ionizing radiation and UV radiation.
- Biological carcinogens
The biological carcinogens include oncogenic viruses. All viruses reproduce by introducing their DNA into the genetic material of the host. Some of them introduce together with it genes that cause uncontrolled growth and multiplication of the infected cell. In this way, they lead to the formation of a neoplastic lesion. It is estimated that 15% of malignant tumors in humans are caused by tumor mutations caused by oncoviruses.
An example of an oncogenic virus is HPV, which increases the risk of cervical cancer. A vaccine against HPV is now available to protect against this carcinogen.
Other oncoviruses:
- HHV -8 - herpesvirus 8 (Kaposi's sarcoma virus)
- HBV - hepatitis B virus
- HCV - Hepatitis C virus
- EBV - Epstein-Barr virus
Does every cancer mutation lead to cancer?
Changes in DNA appear quite often. They arise spontaneously or as a result of the action of carcinogenic factors. Most of the damage is removed by intracellular repair mechanisms.
If the changes are too serious, the cell is directed to apoptosis, ie programmed suicide death. The purpose of this process is to remove defective cells. If this mechanism does not work, the neoplastic process will develop.
When neoplastic mutations lead to neoplastic lesions?
When the mutation affects genes encoding proteins responsible for DNA repair and genome stability, many new damages arise ingenetic material. In such a situation, many different neoplastic mutations arise.
In such an altered cell, the mechanisms that control the cycle of division as well as the mechanism of programmed death are compromised. With successive mutations, the instability of the genome increases, which means that new lesions appear faster.
The situation leads to the loss of homeostasis as well as the acquisition of the features of the neoplastic phenotype. This means that damaged cells look different than he althy cells and cease to perform physiological functions in the body.
Cancer is multi-gene diseases. This means that a single mutation does not directly cause a neoplastic change. Pathological processes in cells and tissues take place when, as a result of an initiating mutation, subsequent mutations arise, which together lead to the loss of control over multiplication and programmed death.
Hereditary cancer mutations
It is estimated that 5-10% of all cancer cases are associated with an inherited genetic predisposition. This is due to the fact that mutations can be passed on across generations. Having a defective gene only increases the likelihood of developing the disease, because cancers are multigene diseases.
An example may be a damaged BRCA1 gene, which increases the risk of breast cancer.
Another example is abnormal RB associated with retinoblastoma. This does not mean, however, that we are dealing with a hereditary form of cancer.
Cancer is caused by many overlapping mutations, not one damaged gene.
About the author
Sara Janowska, MA in pharmacyPhD student of interdisciplinary doctoral studies in the field of pharmaceutical and biomedical sciences at the Medical University of Lublin and the Institute of Biotechnology in Białystok. A graduate of pharmaceutical studies at the Medical University of Lublin with a specialization in Plant Medicine. She obtained a master's degree defending a thesis in the field of pharmaceutical botany on the antioxidant properties of extracts obtained from twenty species of mosses. Currently, in his research work, he deals with the synthesis of new anti-cancer substances and the study of their properties on cancer cell lines. For two years she worked as a master of pharmacy in an open pharmacy.
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