Question

Which of the following mutations is most likely to contribute to the development of cancer?

• A. Loss-of-function mutation in a tumor suppressor gene.
• B. Gain-of function in a DNA repair enzyme.
• C. Silent mutation in a proto-oncogene.
• D. Deletion of non-coding intronic regions in a tumor suppressor gene.

Hint:

Remember the car analogy for cancer genetics:

\textbf{Proto-oncogenes} are the accelerator. Cancer mutation is a \textbf{gain-of-function} (accelerator stuck down).
\textbf{Tumor suppressor genes} are the brakes. Cancer mutation is a \textbf{loss-of-function} (brakes fail).

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Cancer is a disease of uncontrolled cell proliferation, often caused by mutations in genes that regulate the cell cycle. The two main types of genes involved are proto-oncogenes and tumor suppressor genes.
Step 2: Detailed Explanation:
Let's evaluate how each mutation would affect cancer risk:

(A) Loss-of-function mutation in a tumor suppressor gene: Tumor suppressor genes (e.g., p53, Rb) act as the "brakes" of the cell cycle, stopping division if there is DNA damage. A loss-of-function mutation is like having faulty brakes. This allows cells with mutations to continue dividing, leading to cancer. This is a very common mechanism in cancer development.

(B) Gain-of function in a DNA repair enzyme: DNA repair enzymes fix mutations. A "gain-of-function" would mean the enzyme works better or more efficiently. This would lead to fewer mutations being propagated, which would {decrease} the risk of cancer, not increase it.

(C) Silent mutation in a proto-oncogene: Proto-oncogenes are the "accelerators" of the cell cycle. They need a "gain-of-function" mutation to become oncogenes and promote cancer. A silent mutation, by definition, does not change the amino acid sequence of the protein, so it would not alter the protein's function and would not contribute to cancer.

(D) Deletion of non-coding intronic regions in a tumor suppressor gene: Introns are removed from the mRNA transcript before translation. Deleting an intron would likely have no effect on the final protein, unless the deletion affects critical splice sites or regulatory sequences. This is far less likely to cause a loss of function compared to a mutation directly within a coding region (exon).

Step 3: Final Answer:
The most likely mutation to contribute to cancer from the given options is a loss-of-function mutation in a tumor suppressor gene, as it removes a crucial control point for cell division.