Question

1. The following questions are in regard to loss of heterozygosity [LOH].

a) Illustrate the process of LOH making certain to show what happens in the parent and the two daughter cells.

b) Explain why LOH is more likely to result in tumor suppressor gene inactivation in a cell as compared to independent sporadic mutations.

Answer 1

The loss of heterozygosity(LOH) is a common occurrence in cancer, which is indicated by the absence of a functional tumor suppressor gene in the lost region. However, many people remain healthy with such a loss, because there still is one functional gene left on the other chromosome of the chromosome pair. Some tumor suppressor genes have a haploinsufficient phenotype. In animals or humans with one mutant allele and one wild-type allele of a tumor suppressor gene, a suboptimal level of the gene product results in a lower level of function and a loss of fidelity The remaining copy of the tumor suppressor gene can be inactivated by a point mutation in the life of the organism later on, leaving no tumor suppressor gene to protect the body, leading to the manifestation of tumor development. This is the reason why the loss of heterozygosity is a major cause of cancer development.The most commonly known example is the case of development of Retinoblastoma tumours for the loss of function in the RB gene.