Genetics

The Role of Oncogenes in Cancer



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Oncogenes are found in normal cells and encode proteins involved in the control of replication, apoptosis (cell death) or both.  They are involved in the normal function of the cell, but if activated can turn that cell into a cancer cell.


Activation of an oncogene can occur through mutations, rearrangement of chromosomes, or gene amplification.  Mutations can occur for a number of reasons and range from single point mutations where only a single base in the DNA is affected, to larger mutations involving the deletion of part of the gene or an insertion of new genetic material.  They may happen naturally during cell replication or can be caused by an external factor that alters the structure of a nucleotide.  External factors that can cause mutations include carcinogens such as radiation, asbestos, tobacco and a wide variety of other chemicals.  Some viruses can also cause mutations as they insert their genome into the cell's on infection which may alter the structure of the gene, or introduce a promoter leading to overexpression.


Chromosomal rearrangements occur if the DNA double strand becomes broken.  The body naturally repairs this damage, but errors can occur during this process.  Deletions, inversions and translocations are all possible errors in the repair process as the correct broken ends may not be rejoined.  If the break occurred between genes, the gene order of the chromosome will be altered but function will be retained.  If however the break occurred within an oncogene, the resultant rearrangement can cause a mutation or introduce a highly active promoter that leads to the oncogene being activated.  The breakage associated with chromosomal rearrangements is frequently caused by ionizing radiation such as x rays.


Gene amplification occurs when multiple copies of a region of a chromosome are produced during replication.  Each of these copies can be transcribed and translated which results in the protein being overproduced.  If an oncogene is present in the region, the overexpression may result in deregulation of cell growth.


Once activated, oncogenes can lead to cancer.  It is rare for a single activation to cause development of malignancy, with research suggesting that the process involves multiple steps and several oncogenes along with other factors such as tumor-suppressor gene alterations.


The activated oncogene products can be divided into transcription factors, chromatin remodelers, growth factors, growth factor receptors, signal transducers and apoptosis regulators.  Overproduction of many of these can cause increased and unregulated cell division, while mutations in apoptosis regulators prevent the faulty cells from being destroyed as would normally occur.  This leads to the formation of tumors associated with cancer.

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