24. Oncogenes and tumor suppressor genes are termed as cancer-critical genes. Increasingly powerful tools are now available for systematically searching the DNA or mRNAs of cancer cells for either significant mutations or altered expression.

To identify independently an oncogene or a tumor suppressor gene, which of the following would be the most convincing tests to be used?
(1) Transgenic mice that overexpress the candidate oncogene and knockout mice that lack candidate tumour suppressor gene.
(2) Transgenic mice that overexpress the candidate tumor suppressor gene and knockout mice that lack candidate oncogene.
(3) Transgenic mice that overexpress the candidate oncogene and tumor suppressor gene.
(4) Knockout mice that lack the candidate oncogene and tumor suppressor gene.

The most convincing tests to independently identify an oncogene or a tumor suppressor gene are:

(1) Transgenic mice that overexpress the candidate oncogene and knockout mice that lack candidate tumor suppressor gene.

Explanation

• For oncogenes: Overexpression or activating mutations lead to gain-of-function changes that promote cancer. Transgenic mice engineered to overexpress a candidate oncogene can demonstrate whether this gene induces tumorigenesis.

• For tumor suppressor genes: They act by restraining cell growth, and mutations typically cause loss of function. Knockout mice that lack a candidate tumor suppressor gene can be used to test whether its loss leads to increased cancer susceptibility.

This approach mimics the biological effect of activation (oncogenes) and inactivation (tumor suppressors) to confirm their cancer-critical roles.​

• Option (2) is incorrect as overexpression of tumor suppressor genes is usually not oncogenic, and loss of oncogenes isn’t typically tumor-promoting.

• Option (3) overexpressing both may confound the results.

• Option (4) knocking out oncogenes usually does not cause cancer since oncogenes act dominantly in activated forms.