When oncogenes are activated by mutation we most often find that the mutation is

Question

When oncogenes are activated by mutation we most often find that the mutation is a substitution while when tumor suppressor genes are mutated the common mutation is an insertion/deletion. Why is this? p53 is a tumor suppressor gene yet mutations in p53 found in cancers are more often substitutions not insertion/deletions and these mutations are dominate loss of function as opposed the recessive. We call this type of mutation dominate negative, explain what is meant by that terminology. Explain how the inactivation of p53 is different than other tumor suppressors.

Explanation / Answer

why mostly substitution mutation occurs in activation of oncogenes;- See, this is not always the case. Activation of protooncogenes may occur by substitution, insertion/deletion, gene amplification and chromosome rearrgangements.

why mostly insertion/deletion type of mutation occur in tsg:- Tumor suppressor genes represent the opposite side of cell growth control, normally acting to inhibit cell proliferation and tumor development. In many tumors, these genes are lost or inactivated, thereby removing negative regulators of cell proliferation and contributing to the abnormal proliferation of tumor cells. This is mostly achieved by insertion / deletion

Dominant negative mutations are also known as antimorphic mutations. They have an altered gene product that acts antagonistically to wild type allele. It means presence of abnormal allele. ; which consiquently leads to cancer. This is what happens in p53.

Inactivation of p53 different from other tumor suppressors:- Other tumour suppressor genes like Rb(retinoblastoma) involve deletion. Deletion of Rb leads to cancer. In p53 , loss of function is observed or inactivation of the gene occurs. If deletion occurs in p53, then cell cycle arrest will be prevented.

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