What type of mutations usually occur in tumor suppressor genes in malignant cells?
a. Gain of function
b. Loss of function
c. Activating
d. Amplification
The correct answer and explanation is:
Correct Answer:
b. Loss of function
Explanation (300 words):
Tumor suppressor genes are crucial components of the cellular machinery that help regulate cell growth, repair DNA damage, and initiate apoptosis (programmed cell death) when abnormalities are detected. These genes act like the “brakes” of the cell cycle, preventing uncontrolled cell division. Well-known examples include TP53, RB1, and BRCA1/2.
In malignant (cancerous) cells, loss of function mutations are the most common type of mutation found in tumor suppressor genes. This means that the gene product (usually a protein) is either missing or nonfunctional due to the mutation. When these protective mechanisms are impaired, cells can grow uncontrollably, leading to tumor formation.
For a tumor suppressor gene to lose its regulatory effect, both copies (alleles) typically must be inactivated — a concept known as Knudson’s “two-hit hypothesis”. This distinguishes tumor suppressor gene mutations from oncogene mutations, where just one mutated copy is often enough to drive cancer progression.
Let’s clarify why the other options are incorrect:
- a. Gain of function – This is typically associated with oncogenes, not tumor suppressor genes. Oncogenes promote cell growth and division when mutated in a way that increases their activity.
- c. Activating – Similar to gain of function, activating mutations are linked to oncogenes, which encourage malignancy by promoting overactive cellular signaling.
- d. Amplification – Gene amplification also relates to oncogenes, where extra copies lead to increased protein production and heightened growth signals.
In summary, loss of function mutations disable the tumor-suppressing capabilities of these genes, removing key barriers to unchecked cell proliferation and contributing significantly to cancer development. Understanding this mechanism is crucial in cancer biology and targeted therapy development.