THE cells of all living organisms carry within them a microscopic blueprint of life, deoxyribonucleic acid, or DNA. This genetic material stores and regulates essential information governing cell growth, development, structure, maintenance and disease. Human DNA, comprising around 3.2 billion sequences of four chemical bases — adenine, guanine, cytosine and thymine — holds the unique code that determines who we are.
In Homo sapiens, approximately 99.9 per cent of DNA is identical across all individuals. It is the remaining 0.1 per cent, seemingly trivial, that accounts for the vast range of human diversity, from height, weight and eye colour to susceptibility to disease and responsiveness to medication. Within this slender margin lies the essence of heredity, transmitted from parents to children through genes embedded in the genomic fabric.
During this hereditary process, minor changes in DNA’s nucleotide sequences occur naturally. Known as mutations or polymorphisms, these variations are the source of genetic diversity. But when such alterations manifest abnormally, they can form distinct mutation patterns associated with diseases like cancer. By studying these patterns, scientists can now trace how tumours originate, evolve and respond to treatment.
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Unravelling mutational signature
IN ONCOLOGY, researchers have identified a striking phenomenon known as a ‘mutational signature’,Ìý a unique pattern that emerges from studying thousands of tumours and millions of genetic mutations. Each signature reflects the mutational processes active during cancer’s development and indicates the underlying cause of the disease. Every agent capable of damaging DNA, whether chemical, biological, or environmental, leaves behind a recognisable imprint.
By examining these mutation patterns across cancer genomes, scientists can detect DNA repair defects or mutational mechanisms that contribute to tumour formation. Distinguishing between these signatures not only deepens our understanding of an individual’s genome but also guides oncologists towards more targeted and personalised treatment strategies. This approach forms the foundation of what is now known as ‘precision oncology’.
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How mutational signatures arise
MUTATIONAL signatures can develop through various pathways; environmental exposures, internal biological processes and deficiencies in DNA repair mechanisms.
External environmental factors such as cigarette smoke, air pollution, toxic chemicals, harmful viruses, ultraviolet radiation and occupational hazards are major culprits. UV radiation from sunlight, for instance, is a well-established cause of DNA damage, producing characteristic mutational signatures. Similarly, tobacco smoke contains carcinogens that leave distinct genetic scars, particularly visible in lung cancer. According to the American Cancer Society, even individuals who have never smoked may develop lung cancer due to exposure to radon (a radioactive gas), air pollution, or occupational hazards such as diesel and mobile exhaust.
Internal biological processes also play a part. DNA replication, the process by which a cell copies its genetic material, is normally precise, but occasional errors can slip through. These errors may alter genetic information, leading to the production of defective proteins that disrupt normal cellular functions and, in some cases, initiate cancerous growths.
DNA repair deficiencies constitute another critical factor. Cells are equipped with sophisticated repair systems to fix genetic damage, but when these mechanisms fail or the damage proves too severe, mutations accumulate. Such defects may impair proteins responsible for key bodily functions, contributing to the onset of cancers and even neurological or neurodegenerative disorders.
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Promise of precision oncology
EVERY individual with cancer possesses a distinct mutational signature. Decoding this hidden genomic imprint offers remarkable insight into the mechanisms driving a specific cancer and, consequently, the treatment most likely to succeed. This principle underpins precision oncology, a transformative model of cancer care in which therapies are tailored to the genetic profile of a patient’s tumour rather than relying on standardised, one-size-fits-all treatments.
Through genomic analysis, clinicians can identify the precise mutational patterns responsible for malignancy and use this knowledge to predict therapeutic response. Such an approach marks a significant leap forward from conventional cancer treatment, bringing medicine closer to true individualisation.
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Current landscape and future prospects
AT PRESENT, mutational signature analysis remains primarily a research tool, allowing scientists to examine mutation patterns to understand their origins and predict disease outcomes. It has yet to become standard practice in clinical oncology, owing to methodological complexities and the need for further validation. Nevertheless, the field is advancing rapidly, holding immense promise for future applications in diagnosis, prognosis and treatment planning.
If integrated effectively into medical systems, mutational signature analysis could enhance drug efficacy, minimise adverse reactions and reduce healthcare costs associated with ineffective or harmful treatments. This ‘right drug at the right time’ model aligns with the broader vision of precision medicine.
For developing nations, including densely populated countries such as Bangladesh, adopting genomic technologies could significantly improve public health outcomes. It would not only strengthen cancer care and early diagnosis but also contribute to medical education and research capacity, ultimately reducing the economic and psychological burden on healthcare systems and workers alike.
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Sarker M Shaheen is a researcher of neurogenetics and precision medicine in psychiatry, pharmacology and medical genetics department at the University of Calgary, Canada.
