Brightlight
New User
Joined: 28 Mar 2006
Posts: 6
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 Posted: Tue Mar 28, 2006 4:34 am Post subject: Genes and cancer... |
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There haven't been replys to this thread for a little while, but I'll add some basics of gene implication in cancers.
First, it's good to have a grasp of the following three terms:
-Proto-oncogenes: normal genes involved in growth promotion and signaling
-Oncogenes: though sometimes used synonomously with proto-oncogenes, more specifically indicates a mutation to a growth promoting gene resulting in inappropriate expression, such as overexpression or unregulated signaling; they act in a dominant fashion (gain-of-function), requiring only a single copy to be activated
-Tumor suppressor genes: normal genes which control cell proliferation, cell cycle progression, or DNA repair that are inactivated by genetic mutation; act in a recessive fashion (loss-offunction), requiring both copies to be inactivated
Now, cancers aren't inherited diseases, but the defect genes that can be attributed to cancer can be inherited. What this means is that even if you inherit a defective gene, that alone will not cause cancer to develop.
Some examples of oncogenes:
The various ras gene (N-ras, H-ras, k-ras) products are members of a large family of GTPbinding proteins that relay signals from cell surface receptors to the nucleus, and are involved in growth signaling pathways. Mutations in ras genes are found in about 30% of human cancers and can lead to uncontrolled growth signaling. A single point mutation in k-ras is often found in colon cancer; a deletion in N-ras is found in neuroblastomas; a deletion in H-ras is found in many sarcomas.
Another family of genes, myc (N-myc, c-myc), gene products are nuclear mitogens involved in promoting cell-cycle entry. Mutations in myc usually result in verexpression or amplification, sometimes as a result of translocations that bring myc close to promoters, producing excessive amounts of myc mRNA. The myc gene is also involved in the immortilization of cells. A translocation between chromosomes 2 and 8 in c-myc and/or N-myc is commonly found in Burkitt’s lymphoma; a c-myc translocation between chromosomes 8 and 14 is found in B-cell lymphoma; and neuroblastomas often have an amplification in N-myc.
Some examples of tumor suppressor genes:
Loss of both copies of the Rb (retinoblastoma) gene leads to retinoblastoma, a cancer of the developing retina. Spontaneous retinoblastoma is a relatively rare childhood disease, occurring in one in 20,000 children through spontaneous lost of one copy of the gene followed by a spontaneous loss of the second gene in the same somatic cell. In familial retinoblastoma, a mutated copy of the gene is inherited and present in all cells, greatly increasing the chance of loss of the second copy. The Rb protein is involved in regulation of cell cycle progression. Loss of both functional copies of Rb is found in several cancers other than retinoblastoma, including osteosarcomas, lung, breast and prostate cancers.
Probably the most important cancer critical gene is p53, which is multiply involved in DNA damage response, cell cycle control, and apoptotic pathways. Inactivation of both alleles of p53 leads to increased genomic instability, since damaged cells are no longer prevented from reproducing. Loss of p53 is found in many cancers (about 50% of all human cancers have loss of p53 functionality), including colon, breast, cervical, small-cell lung cancer, and bladder, and in Li-Fraumeni syndrome, where p53 mutations are familial. |
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