Abnormal Genes and Cancer
Abnormal Gene and Cancer
Dr.P.K.Ghatak, MD
No.32.
Chemically, the genes are composed of Deoxyribonucleic Acid (DNA). There are four different nucleic acids - they are known as A, T, G & C. AT and GC always appear in pairs and are called Base Pairs. The three of these base pairs make a word of the coded instruction. A gene, on average, contains 17,000 Base Pairs and may contain as many as several million. Human chromosomes carry 3.2 billion base pairs and only 25,000 genes are known to code proteins. We have 23 pairs of chromosomes and we inherit one strand of the chromosome from each parent.
Cell death is programmed into the genes. If and when programmed cell death fails in one cell, this cell continues to live and multiply. This is the beginning of tumor growth and ultimately leads to cancer formation. Errors may appear in the spelling of coded words (Mutation), words may be dropped (Deletion), or attached to a different place (Translocation). The cells of an older person have divided many more times than a younger one and the elderly population is at a higher risk of acquiring abnormal genes (Somatic Mutation). It explains the reason for the increased cancer rate in old age.
A class of genes has the role of a caretaker function called Caretaker Genes. It looks after the entire population of chromosomes. The deficiency of these genes increases the rate of mutation in all genes. Another class of genes, called the Gatekeeper Gene, restrains the growth of individual cells and promotes cell differentiation.
A specific group of cells in our body is constantly keeping a vigil for such mutant cells (Surveillance cells). Once they detect a mutant cell, they mark it with a protein, and Killer cells then move in and promptly remove these mutant cells from the body.
Somatic mutation or an inherited defective gene/chromosome is the immediate cause of cancer. The development of cancer, however, is a failed multi-step process. A mutant cell has a growth advantage over its neighbors, but it must escape from the surveillance cells before it can divide again. When mutant cells have gone through 5 to 10 generations of cumulative mutations, then mutant cells have a chance to establish as a Malignant Phenotype (potential to cause cancer in this individual.
These are cancer causing genes. They were first discovered in certain retrovirus-induced cancers in chickens. Similar genes (homologous genes) are also present in human cells. But they are very tightly controlled by tumor suppressors and caretaker genes. To escape the scrutiny of tumor-suppressed genes and caretaker genes, the oncogenes have to mutate first. There are 3 such mechanisms.
Oncogenes:
1. Translocation: A piece of a chromosome containing specific genes breaks away from its normal location and attaches to a different chromosome, e.g., in chronic myelogenous leukemia, a piece of chromosome 9 is grafted to chromosome 22. This abnormality is better known as the Philadelphia chromosome of CML.
DNA Amplification: A certain part of the base pairs of a gene appears repeatedly over and over again. This is often seen in Sarcoma and aggressive breast cancer.
3. Point mutation: One base pair mutation appears in several gene locations; often present in pancreatic cancer and colon cancer.
When one copy of mutated oncogenes overrides the effect of its other normal copy and the disease is manifested in the person carrying the mutated genes. This mode of inheritance is known as Autosomal Dominant Inheritance. When one copy of the mutated gene does not cause cancer but needs both copies of the gene to be mutated, then this type of inheritance is called the Autosomal Recessive Mode of transmission. One mutated copy is usually inherited; the other may result from a somatic mutation.
This short essay is an abridged portion of my other blog Medical matters: Archive
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