Cancer is thought to be caused by the accumulation of two or more \"hits\" - tha

Question

Cancer is thought to be caused by the accumulation of two or more "hits" - that is, two or more mutations that affect cell proliferation and survival in the same cell. many of these oncogenic mutations are dominant; one mutant copy of the gene is sufficient to change the proliferative properties of a cell.

which of the following general types of mutations have the potential to create dominant oncogenes? (justify each answer)

# A mutation that increases the number of copies of a transcriptional activator of a cell cycle promoting gene; or a nonsense mutation located shortly after the beginning of translation in a gene that encodes a growth- factor receptor

Explanation / Answer

A mutation that increases the number of copies of a transcriptional activator of a cell cycle promoting gene is the right option : Tumor cells also can arise by non-genetic means through the actions of specific tumor viruses. Tumor viruses are of two distinct types. There are viruses with DNA genomes (e.g. papilloma and adenoviruses) and those with RNA genomes (termed retroviruses). RNA tumor viruses are common in chickens, mice and cats but rare in humans. The only currently known human retroviruses are the human T-cell leukemia viruses (HTLVs) and the related retrovirus, human immunodeficiency virus (HIV). Retroviruses can induce the transformed state within the cells they infect by two mechanisms. Both of these mechanisms are related to the life cycle of these viruses. When a retrovirus infects a cell its RNA genome is converted into DNA by the viral encoded RNA-dependent DNA polymerase (reverse transcriptase). The DNA then integrates into the genome of the host cell where it can remain being copied as the host genome is duplicated during the process of cellular division. Contained within the sequences at the ends of the retroviral genome are powerful transcriptional promoter sequences termed long terminal repeats (LTRs). The LTRs promote the transcription of the viral DNA leading to the production of new virus particles. At some frequency the integration process leads to rearrangement of the viral genome and the consequent incorporation of a portion of the host genome into the viral genome. This process is termed transduction. Occasionally this transduction process leads to the virus acquiring a gene from the host that is normally involved in cellular growth control. Because of the alteration of the host gene during the transduction process as well as the gene being transcribed at a higher rate due to its association with the retroviral LTRs the transduced gene confers a growth advantage to the infected cell. The end result of this process is unrestricted cellular proliferation leading to tumorigenesis. The transduced genes are termed oncogenes. The normal cellular gene in its unmodified, non-transduced form is termed a proto-oncogene since it has the capacity to transform cells if altered in some way or expressed in an uncontrolled manner. Numerous oncogenes have been discovered in the genomes of transforming retroviruses. The second mechanism by which retroviruses can transform cells relates to the powerful transcription promoting effect of the LTRs. When a retrovirus genome integrates into a host genome it does so randomly. At some frequency this integration process leads to the placement of the LTRs close to a gene that encodes a growth regulating protein. If the protein is expressed at an abnormally elevated level it can result in cellular transformation. This is termed retroviral integration induced transformation. It has recently been shown that HIV induces certain forms of cancers in infected individuals by this integration induced transformation process. Cellular transformation by DNA tumor viruses, in most cases, has been shown to be the result of protein-protein interaction. Proteins encoded by the DNA tumor viruses, termed tumor antigens or T antigens, can interact with cellular proteins. This interaction effectively sequesters the cellular proteins away from their normal functional locations within the cell. The predominant types of proteins that are sequestered by viral T antigens have been shown to be of the tumor suppressor type. It is the loss of their normal suppressor functions that results in cellular transformation. back to the top

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