20.10: Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.

When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell cycle. It's only when both the copies of the gene are inactivated or lost that the cells lose control and become cancerous.

Some common tumor suppressor genes that have implications in human cancer include TP53, Rb, INK4, PTEN, APC, BRCA1/BRCA2, and MADR2. Loss of function mutations in these tumor suppressor genes has implications in many types of cancers, including ovarian, lung, colorectal, head and neck, pancreatic, uterine, breast, and bladder cancer.

In a healthy cell, tumor suppressor genes act as the gatekeepers that control cell growth and proliferation and promote cell apoptosis.

Hence, when a tumor suppressor gene is inactivated, cells may start growing out of control leading to cancer.

Fortunately, in most cases, the inactivation of a single allele of a tumor suppressor gene does not lead to tumor progression. Both of the alleles must lose their function for the cells to become cancerous.

Such loss of function mutations in tumor suppressor genes can be caused by genetic alterations such as point mutations,  chromosomal deletion,  or errors in chromosome segregation.

However, a few epigenetic changes can also permanently inactivate the tumor suppressor genes. For example, if a gene undergoes modifications in its promoter region or gets packaged into the heterochromatin region of a chromosome, it can make irreversible and heritable changes to the gene expression pattern.

• Tumor Suppressor Genes - They slow down cell division, repair DNA mistakes, and program cells for apoptosis.
• Function of Tumor Suppressor Genes - This is to manage cell division and repair DNA errors.
• Mutations Development - This is when the function of tumor suppressor genes fails, resulting in uncontrolled cell growth.
• Single Functional Copy of the Gene - It helps cells maintain their normal functions and cell cycle.
• Common Tumor Suppressor Genes - Notable examples include TP53, Rb, INK4, PTEN, APC, BRCA1/BRCA2, and MADR2.

• Define Tumor Suppressor Genes – Explain the role and function in cell division and DNA repair (e.g., TP53, Rb, INK4).
• Contrast Healthy vs Mutated Genes – Describe the difference in functions and impact on cell behavior (e.g., gene mutation vs healthy).
• Explore Examples – Talk about specific tumor suppressor genes and their role (e.g., PTEN, APC, BRCA1/BRCA2).
• Explain Mutation Effect – Describe the outcome when both copies of the gene are inactivated or lost.
• Apply in Context – Discuss the connection between defective tumor suppressor genes and cancer development.

• What are Tumor Suppressor Genes and what is their function?
• What happens when these genes develop mutations?
• What is the role of common tumor suppressor genes in different types of cancers?

• Students – Gain insights on genetic components and their functions, enhancing biology knowledge.
• Educators – Provides a clear framework to teach about genetics and cancer development.
• Researchers – Importance of tumor suppressor genes in studying cancer development and genetic therapy.
• Science Enthusiasts – Offer insights into the complex world of genetics and its impact on human health.