LUNG CANCER: Genetic Signatures

wellcome-images

Fig: A DNA Double Helix model (flickr.com/creativecommons)

Lung Cancer is a group of diseases which are not easily detected due to diverse the nature of their manifestation. There are no specific and dependable biomarkers (molecules that signify disease) present in the blood or tissues which could be used to confirm the existence of the disease in all of its manifestations. However, genetics is a very important tool that can be employed in the tracking, detecting and treatment of lung cancer especially at the early stages.

Genetics is the study of genes. Genes are codes on DNA which express characteristics of organisms. The DNA is a double strand formed out of molecules called nucleotide bases which complement each other on the opposite side of the strands. There are four nucleotides in the DNA strands: Guanine (G), Adenine (A), Cytosine (C) and Thymine (T). Guanine (G) usually complements with Cytosine (C) while Adenine (A) usually complements with Thymine (T). The different combinations of these nucleotide bases code for specific amino acids which in turn are joined together to form proteins which are the building blocks of life and are important in the formation of enzymes and hormones. A group of nucleotide bases arranged to code for a certain protein on a DNA strand is called a gene. The body manufactures proteins on a need to need basis as required by the cells and the tissues. For example, when one has an injury, the DNA in the cells around the injured area may code for the manufacture of specific proteins such as melanin (skin pigment) to be able to accelerate recovery from the wound.

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Fig: Representation of nucleotide base sequence as depicted (Photo by Miki Ashihito through flickr.com/creativecommons)

Sometimes however, genetic expressions on the DNA may be altered due to a person’s heritage (family line) or environmental factors e.g. chemicals such as aflatoxins, aromatic hydrocarbons and radioactivity which can alter the expression of certain genes, also known as gene mutation. When gene mutation occurs, the coding of some proteins can be exaggerated or suppressed leading to the development of diseases like cancer.

In lung cancer, some proteins which are located on the lung cell walls may be affected by this genetic disorder and are crucial in the understanding of the disease.

EGFR (Epidermal Growth Factor Receptor)

EGFR is a protein that doubles up as an enzyme. It is found on the surface of healthy cells and is crucial in the process of cell division. It is encoded in the EGFR gene on the DNA. Genetic mutations on the DNA strand may lead to an over-expression of this gene leading to the synthesis of excessive EGFR resulting into excessive and abnormal cell division. About 15% of patients with Non Small Cell Lung Cancer exhibit mutations of this gene (24). EGFR belongs to a group of enzymes known as Tyrosine Kinases which are very important in cell division. In Lung Cancer treatment, substances known as ‘Tyrosine Kinase Inhibitors’ or TKI are employed in the control of excessive and abnormal cell division.

ALK (Anaplastic Lymphoma Kinase)

ALK is also a protein which functions as an enzyme and is found on the cell surface and is also responsible for cell division belonging to the class enzymes called Tyrosine Kinases. It is coded by the ALK gene on the DNA. Gene mutation leads to an over- expression of its code leading to its excessive synthesis and promotion of rapid and abnormal cell division in the body. About 3-7% of lung cancer patients display this gene mutation especially among smokers and non- smokers who are young (25). Its cancerous nature can be suppressed by Tyrosine Kinase Inhibitor drugs.

KRAS (Kirsten Rat Sarcoma) Viral Oncogene Homolog

KRAS is a protein which functions as an enzyme in healthy cells. It belongs to a group of enzymes called the GTPases which are also very important in cell division. It is encoded by the KRAS gene on the DNA which is also known as an oncogene (genes expressing proteins that are very key in cell division). A mutation of this gene may lead to production of excessive KRAS in the cells leading to abnormal cell division and cancer. KRAS gene mutation is usually expressed in about 15- 20% of Non Small Cell Lung Cancer (NSCLC) patients with the Adenocarcinoma variety.

Genetic mutations of can be detected in a biotechnological or biochemistry lab by using methods such as FISH (Fluorescent In- Situ Hybridization) as approved by the US Food and Drug Administration. It involves the labeling of specific genes on DNA extracted from a patient with light- emitting substances and reacting them with healthy DNA in order to mark out the over-expressed or missing genes for disease diagnosis.

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Fig: Fluorescent In-Situ Hybridization (FISH) technique displaying genetic mutations as emitted light (Photo by Wellcome Images through flickr.com/creativecommons)

DISCLAIMER: The information in this article is written for general information purposes and MUST NOT be used as a substitute for personalized medical care from a qualified medical practitioner. This blog platform will not be responsible for any injury or damage to persons of property arising from any errors or omissions.

 

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Author: nanosphereblog

John Mmbaga is a graduate of B.Sc (Biochemistry and Chemistry) from Kenyatta University in Nairobi, Kenya. He is currently pursuing an M.Sc in Environmental Chemistry at the University of Nairobi. He has a combined working experience of over 10 years in the Corporate, Non Profit and Agricultural sectors in Kenya, having worked at various positions including but not limited to managerial and business ownership. He also has been a recipient of funding from the National Commission for Science Technology and Innovation (Currently- National Research Fund) in Kenya for his post graduate work on the ‘Design and fabrication of polymer- layered silicate nanocomposites for water remediation’. He has interests in nanocomposite materials for water treatment and purification, electrochemical sensors for water pollutant detection, sensors in medical diagnostics, nanotechnology in energy conversion and applications of nanotechnology in agriculture. He also has attended a short Course on ‘Nanotechnology and Nano-sensors’ at the Technion University, Haifa, Israel among other short courses. He has an immense passion for communicating about nanotechnology and its capacity to solve African developmental problems especially in the fields of Agriculture, Healthcare, Energy and Environmental degradation.

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