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:
  • Abl
  • Src
  • H-ras
  • N-ras
• Nuclear DNA binding protein:
  • Myc
  • N-Myc
• 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

• Cancer
• Genetics

References and further reading