Genetics of cancer
Cancer is a genetic disorder in which the normal control of cell growth is lost. Cancer genetics is now one of the fastest expanding medical specialties. At the molecular level, cancer is caused by mutation(s) in DNA, which result in aberrant cell proliferation. Most of these mutations are acquired and occur in somatic cells. However, some people inherit mutation(s) in the germline.[1] The mutation(s) occur in two classes of cellular genes: oncogenes and tumor suppressor genes.
Transformation of proto-oncogene to oncogene[2] is the result of gain in function through:
- Over-expression of the gene, or duplication (such as amplification) to produce increased onco-protein
- Activation or formation of fusion gene by translocation
- Alteration of the gene product to produce transforming proteins
Examples of Oncogenes
- Signal transduction proteins:
- Nuclear DNA binding protein:
- Secreted growth factors:
- Sis
- Growth factors cell-surface receptors:
- Erb-A
Tumor suppressor genes
Under normal conditions, tumor suppressor genes regulate cellular differentiation and suppression of proliferation. Mutations in these genes result in unchecked cellular proliferation resulting in tumors with abnormal cell cycles and tumor proliferation. The tumor suppressor genes contribute to cancer by the inactivating of loss of function mutation.
Examples of tumor suppressor genes
- p53
- RBI
DNA repair genes
DNA damage does occur in cells and if not repaired, can result in mutations. DNA repair genes code for enzymes that are responsible for fixing these damages. Inability to fix these damages often results in genome instability where mutations accumulate and get passed down to daughter cells.[3] These mutations may disrupt the proper function of cell division, namely the genes that control the cell cycle, which promotes tumor development. Increasing evidence suggests mutations in these genes that regulate recognition and repair of DNA damage are critical in tumorigenesis. DNA repair genes are often affected by loss of function mutations.
See also
References and further reading
- ^ Fiona Lalloo. Genetics of Oncologists. ISBN 1901346196. remedica Publishing
- ^ Robert F. Mueller AND Young I.D.Emery's Elements of Medical Genetics. ISBN 0 443 07125 X
- ^ Hui, T.; Zhen, G.; HuiZhong, L.; BaoFu, Z.; Gang, W.; Qing, Z.; DongSheng, P.; JunNian, Z. (2015), "DNA damage response – A double-edged sword in cancer prevention and cancer therapy", Cancer Letters, 358 (1): 8–16, doi:10.1016/j.canlet.2014.12.038, PMID 25528631