Question

Describe the normal cellular functions of tumor suppressor genes and explain their roles in cancer. List all possible mechanisms by which tumor suppressor genes are inactivated and explain. Explain why loss-of-heterozygosity of a particular chromosome/chromosomal region in tumor DNA suggests the existence of a tumor suppressor gene in that region.

Please type answer, hard to read handwriting on written responses.

Answer 1

A. Function tumour suppressor gene and role in cancer

Tumour suppressor gene is anti-oncogene that regulates a cell division and replication.

The function of Tumor suppressor genes are

1. Slow down cell division
2. DNA repair
3. Apoptosis or programmed cell death.

Role in cancer - Tumor suppressor genes has the major function of apoptosis, if the tumour suppressor genes are non-functional/ inactivated then it will affect apoptosis. If there is no apoptosis then the cells will not die hence there will be the formation of the tumour due to aggregation of old as well as new cells, this will eventually lead to cancer. The cells that can grow out of control develops a  cancer condition.

B. Mechanism of inactivation of Tumor suppressor genes

Tumour suppressor genes are inactivated by different mechanisms. Mutant allele is a leading mechanism of inactivation of the tumour suppressor gene.

Types of mutation - Deletions, nonsense mutations, frame-shift mutations, insertions and missense mutations leads to inactivation of tumour suppressor genes.

Mechanisms

1. Deletion - Deletion is the mutation that is caused by the deletion of one or more nucleotides from the DNA sequence. Deletion in Tumor suppressor genes leads to loss of function of the proteins encoded by these genes this contributes to malignant transformation of cells.

2. Point mutation - A point mutation is termed as the mutation that has affects on single-nucleotide of nucleic acid. A point mutation in tumour suppressor genes can also lead to cancer.

3. Loss of heterozygosity - Loss of heterozygosity is a phenomenon in which the entire gene is a loss. The loss of heterozygosity leads to cancer due to the absence of a functional tumour suppressor gene in the lost region.

4. DNA methylation - Methylation on the promoter regions of tumour suppressor genes can cause gene silencing and methylation, this can induce mutation.

C. Loss of heterozygosity (LOH)

It is the genetic mutation in which one normal copy of a gene or a group of genes is lost. LOH of particular genes leads to the progression of specific cancer types like colorectal cancer and small-cell lung cancer. Cancerous cells have different types of genetic changes, LOH in one or more genes is one of the changes that occur in cancer. If tumour suppressor genes are absent or nonfunctional due to LOH, the normal cell will divide that forms an abnormally and that will eventually lead to cancerous.