From Wikipedia, the free encyclopedia

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.

Oncogene

Oncogenes are derived from normal cellular genes called proto-oncogenes. Proto-oncogenes were first elucidated in RNA tumor viruses and are now known to encode proteins that are crucial for cellular growth regulation (e.g. growth factor, cell-surface receptors, DNA binding proteins, etc.) Mutation in cancer cells alter the normal structure and/or expression pattern of the proto-oncogene, generating oncogenic variant forms with altered function. In genetic terms, oncogenic alleles have gain of function mutation.

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. Mutation 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

Increasing evidence suggests mutation in genes that regulate recognition and repair of DNA damage are critical in tumorigenesis. These DNA damage recognition and repair genes could be considered a unique class of cancer. DNA repair genes are affected by loss of function mutation.

See also

• Cancer
• Genetics

References and further reading

From Wikiversity

Readings

• Study guide:
• Wikipedia article: Oncogenes

Genetics of Cancer

Dominant Mutations in Oncogenes

Dominant mutations in oncogenes usually disrupt or constitutively activate signaling pathways that inform the cell about its environment. A mutation in an oncogene protein or a large excess of the normal protein makes it insensitive to upstream members of the pathway, which leads to constitutive activation of the pathway and unrestrained proliferation. These mutations are usually not inherited and arise during somatic growth.

Oncogenes can also be activated by insertion of a retrovirus at a nearby chromosome location.

Recessive Mutations

Tumor Suppressor Genes

Tume suppressor gene mutations are mutations in signaling pathways or cell cycle progression which regulate cell cycle production. This type of cancer appears to be inherited as a dominant trait even though the original mutant is recessive.

File:Retinoblast.jpg

p53 Mutations

P53 is a tumor suppressor gene. P53 functions as a checkpoint to prevent commitment to S phase if there is unrepaired DNA damage. If there is unrepaired damage, p53 activates production of the p21 gene and this prevents the cyclin/cdk complex from initiating S. If the damage remains unrepaired, p53 causes apoptosis in the cell, eliminating potential mutagenic effects.[[Category:Oncology