Cancer Genetics

Cancer as a Genetic Disease
- Cancer is a genetic disorder at the somatic cell level, caused mainly by mutations in somatic cells (only 5% linked to germ-line mutations).
Genetic Defects in Cancer Cells
- Cancer cells exhibit genetic defects affecting genomic stability, DNA repair mechanisms, and chromatin modifications, leading to tumorigenesis.
Cell-Cycle Regulation
- Alterations in cell-cycle regulation are notable in cancer cells, affecting their growth and division.
Role of Proto-Oncogenes and Tumor-Suppressor Genes
- Cancer is associated with mutations in proto-oncogenes (which promote cell growth) and tumor-suppressor genes (which regulate cell cycle).
Metastasis
- Cancer cells have the ability to metastasize, invading other tissues ultimately affecting overall health.
Genetic Predisposition
- Some cancers can be inherited, indicating a genetic predisposition.
Contribution of Viruses
- Certain viruses are known to contribute to cancer in both humans and animals.
Environmental Factors
- Various environmental agents can cause human cancers, including carcinogens.

Genomic Alterations: Includes single-nucleotide substitutions, chromosomal rearrangements, amplifications, and deletions.
Somatic Mutation: Cancer is caused primarily by mutations that occur in somatic cells rather than being inherited.
Characteristics of Cancer Cells:
- Unregulated Proliferation: Cancer cells demonstrate uncontrolled cell growth and division.
- Metastasis: Cancer cells have the ability to spread to other tissues.

Benign Tumors: Formed by unregulated growth but do not invade other tissues; can usually be removed by surgery without serious harm.
Malignant Tumors: Formed by cancer cells that have metastasized, causing severe health issues.

All cancer cells within a tumor arise from a common ancestral cell that accumulated various mutations, showing that cancer is a clonal disease.

Driver Mutations: Provide a growth advantage to cancer cells; relatively few in number (2 to 8 total).
Passenger Mutations: Do not directly contribute to cancer phenotype and accumulate over time due to high DNA damage in cancer cells.

Proposes that most cells within a tumor are not proliferative. Instead, a subset of cancer stem cells drives tumor growth and has self-renewal capacity.

Cancer development is a multistep process necessitating multiple mutations that accumulate over time, primarily influenced by age and environmental factors.
Carcinogens: Agents that induce mutations in proto-oncogenes or tumor-suppressor genes. Example: radiation leading to leukemia shows a delay between exposure and the onset of disease, indicative of the multistep process.

The formation of malignant tumors stems from genetic alterations that allow cells to escape normal regulatory mechanisms governing cell growth.

Tumor-Suppressor Genes:
- Example: APC Gene - associated with colorectal cancer; inactivating mutations lead to polyp formation.
Proto-Oncogenes:
- Example: Ras - frequently mutated leading to abnormal cell signaling and increased proliferation.
p53:
- Most commonly mutated gene in cancers; plays a crucial role in the cell cycle and apoptosis regulation; inability to function in damaged cells allows proliferation.

Involves cancer cells breaking down extracellular matrix components, potentially entering the lymphatic or blood circulatory system.
Only a small fraction of cells can form secondary tumors; this process is regulated by numerous gene products.

Carcinogens include natural and man-made agents such as tobacco smoke, UV radiation, certain viruses, and dietary components.
Chronic exposure to some agents increases cancer risk significantly.