The genetics behind cancer
Now before I begin this topic I must point out that genetics and cancer are two very complex and detailed areas of human biology. So you can understand that when you couple genetics and cancer together things can become even more complex and difficult to grasp. During my time I have stumbled across numerous textbooks solely devoted to cancer genetics, so to provide an in-depth review of cancer genetics in one post would be an impossible task. My aim is to provide a brief summary of the key players in cancer genetics and hopefully to provide you with the starting point for you to undertake further research.
Cancers result from a series of somatic mutations and in certain conditions there may be an underlying hereditary predisposition. One of the reasons why cancer genetics can be so confusing is due to the fact that mutations in several different genes, that interact with in a variety of different complex pathways can all lead to the development of cancer. Cancer genetic research has enabled the identification of two classes of genes which have been implicated in cancer.
Oncogenes
These are genes that are implicated in causing cellular growth. Within cancers and tumours, oncogenes are overactive as a result of mutations and thus promote cellular proliferation commonly seen within cancers. In the normal non mutated form oncogenes are referred to as proto-oncogenes.
So how do proto-oncogenes from oncogenes that contribute to cancers. Well they can be activated through point mutations; this is typical of the RAS family of genes. These genes are involved in cell signalling and are commonly involved in melanomas and lung cancers. They can also be activated via amplification of oncogenes; this is seen in the ERBB2 gene and this is commonly seen in breast cancers. Other mechanisms include chromosomal translocations and rearrangements.
Tumour suppressor genes
As there name suggest these genes act to suppress the various steps that lead to cancer development. In tumour and cancerous cells these genes are mutated and thus cannot serve their function thus further promoting cancer cell proliferation.
Knudson was a key player in the research surrounding tumour suppressor genes. Retinoblastoma is a cancer of the retina that occurs during childhood. This cancer is caused by mutations in both copies of the RB1 gene. This is where Knudson developed his two hit hypothesis. Stating that two mutations are needed for the disease state and in familial conditions one of these hits is already inherited. These genes are tumour suppressor genes and both copies are needed to become inactive in order to cause the cancer state.
Genomic instability
A common feature of all cancers is the increase in genomic instability. This instability seen in the genome is possibly one of he reasons why the mutations rate in individuals with cancers is much more elevated. Some of the features of genomic instability include the loss of the spindle checkpoint. This checkpoint ensures that all chromosomes are attached to spindles as to prevent improper segregation.
Furthermore genes such as ATM, BRCA1 and BRCA2 can also be implicated in eventual genomic instability. These are tumour suppressor genes and help to inhibit the events that lead up to cancer states.
ATM is a part of a complex that is involved in detecting damage. ATM upon detecting damage is involved in widespread cell signalling. BRCA1 is a protein that is involved in recombination and was the first gene to be linked to hereditary breast cancer. BRCA2 has a very similar roles I to BRAC1 in that it is involved recombination, transcription regulation and also plays a role in epigenetic modification such as chromatin remodelling.
Telomeres have also been linked to cancers. These are structures that cap the ends of telomeres and are made up of repetitive sequences. It has been suggested that in cancers these structures are at a point of crisis because of their short length, and instead of the cell entering a process of cell death they become genomically unstable and become immortal through the activation of telomere maintenance mechanisms.
Conclusion
These are just some of the genetic pathways which can lead to cancers. There are many others and with advances in genotyping and gene detection numerous other genes and pathways have been identified. With the invention of microarrays it is also hoped now that we can develop expression profiles which outline the various genes that are inactivated and activated in various tumours. From all this maybe we can one day develop a cure for this devastating disease.
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