Question

What is loss of heterozygosity, and how does this process contribute to the development of cancers?

Short answer

Answer: Loss of heterozygosity (LOH) is a genetic event that leads to the loss of normal function of one of the two alleles of a gene, leaving only one functional allele. LOH can occur through various mechanisms, such as deletion, duplication, or genetic recombination. It contributes to the development of cancers by disrupting the function of tumor suppressor genes, which are essential for regulating cell growth and division and preventing malignant tumors. When LOH occurs and a functional tumor suppressor gene allele is lost, the gene's activity is compromised, potentially leading to uncontrolled cell proliferation and cancer development. This process is called the "two-hit hypothesis," wherein two genetic events, mutation and LOH, are required for cancer development.

Step-by-step solution

Define Loss of Heterozygosity

Loss of heterozygosity (LOH) is a genetic event that leads to the loss of normal function of one of the two copies, or alleles, of a gene, leaving only one functional allele. This can occur through various mechanisms, such as deletion of a chromosomal region, duplication of the remaining allele, or genetic recombination.

Explain Genetic Mechanisms that Cause LOH

LOH can occur through several genetic mechanisms: 1. Deletion: A chromosomal region containing the functional allele is removed, resulting in the loss of one copy of the gene. 2. Duplication: The remaining non-functional allele is duplicated, rendering the cell homozygous for the non-functional allele. 3. Genetic recombination: During DNA replication or repair, the non-functional allele is 'swapped' with the functional allele from the other homologous chromosome, resulting in homozygosity for the non-functional allele.

Introduce the Role of Tumor Suppressor Genes

Tumor suppressor genes are essential genes that regulate a cell's growth and division and help prevent the formation of malignant tumors. They encode proteins that are involved in DNA repair, cell cycle regulation, and apoptosis, which prevent uncontrolled cell proliferation. Having a functional copy of a tumor suppressor gene is crucial for maintaining normal cellular function and preventing cancer.

Explain How LOH Contributes to Cancer Development

Loss of heterozygosity contributes to the development of cancers by disrupting the function of tumor suppressor genes. Many cancers are associated with mutations in tumor suppressor genes that render them non-functional. In these cases, having one functional and one non-functional allele might still provide enough tumor suppressor activity to prevent cancer development. However, when LOH occurs, and the functional allele is lost, the tumor suppressor gene's activity is compromised, and cancer can develop. This is known as the "two-hit hypothesis," in which two genetic events (mutation and LOH) are required for cancer development.