How does cancer differ from most other genetic disorders
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How Cancer Differs from Most Other Genetic Disorders
Somatic vs. Germline Mutations in Cancer
One of the primary distinctions between cancer and most other genetic disorders lies in the nature of the mutations involved. Cancer is predominantly a somatic disease, meaning it arises from mutations that occur in non-reproductive cells during a person's lifetime. These somatic mutations contrast with germline mutations, which are inherited and present in every cell of the body from birth . This somatic nature allows cancer to affect highly constrained genes that are crucial for basic cellular functions such as cell proliferation, differentiation, and genomic integrity maintenance.
Multistep Mutation Process in Cancer
Unlike many genetic disorders that may result from a single genetic mutation, cancer typically requires multiple mutations to develop. This multistep process involves several genetic changes that drive waves of cellular multiplication, leading to gradual increases in tumor size, disorganization, and malignancy . It is estimated that three to six mutations are necessary to complete the transformation from a normal cell to a malignant one.
Epigenetic Alterations in Cancer
Cancer is also unique in its significant reliance on epigenetic changes, which are modifications that affect gene expression without altering the DNA sequence. These epigenetic disruptions can occur in stem/progenitor cells and contribute to tumor heterogeneity and progression. This epigenetic plasticity, combined with genetic lesions, drives the development and evolution of cancer. Non-neoplastic but epigenetically disrupted cells may thus be crucial targets for cancer risk assessment and chemoprevention.
Functional Centrality and Evolutionary Constraint of Cancer Genes
Cancer genes are more functionally central and evolutionarily constrained compared to genes involved in other genetic disorders. This means that cancer genes play more critical roles in cellular functions and are subject to stronger evolutionary pressures to maintain their integrity. Both somatic and hereditary cancer genes are more functionally central than genes contributing to non-cancer genetic disorders. However, somatic cancer genes tend to be more evolutionarily constrained than hereditary cancer genes, highlighting the unique impact of somatic mutations in cancer.
Role of Oncogenes and Tumor Suppressor Genes
Cancer involves the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Oncogenes, which are mutated forms of normal genes, drive cell proliferation and differentiation, while tumor suppressor genes are involved in the negative control of cellular proliferation. The interplay between these genetic alterations is crucial in the multistep process of tumor formation .
Conclusion
Cancer stands out among genetic disorders due to its somatic nature, multistep mutation process, significant epigenetic alterations, and the critical roles of oncogenes and tumor suppressor genes. These unique characteristics underscore the complexity of cancer and the necessity for targeted approaches in its diagnosis, treatment, and prevention. Understanding these distinctions is essential for advancing cancer research and improving patient outcomes.
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