Cancer Genetics Chapter 11

Study Notes

Cancer is a prevalent and deadly disease, causing approximately one in four deaths worldwide.
One in two people is expected to be diagnosed with invasive cancer in their lifetime.
Cancer arises from a combination of environmental exposures and genetic mutations.

Uncontrolled cell proliferation, culminating in tumor formation (neoplasm).
Tumorigenesis involves:
- Heightened growth signals
- Resistance to growth-inhibiting cues
- Evasion of apoptosis
Tumors require a fresh blood supply acquired through angiogenesis.
Malignant tumors infiltrate nearby tissues and disseminate to distant body sites (metastasize).

Categorized based on their tissue of origin:
- Sarcomas (mesenchymal tissue, such as bone, muscle, or connective tissue)
- Carcinomas (epithelial tissue, such as cells lining the intestine, bronchi, or mammary ducts)
- Hematopoietic and lymphoid malignant neoplasms (leukemia and lymphoma, arising in cells of hematopoietic lineage)

Genetic alterations of cell regulatory systems are the primary basis of carcinogenesis.
Cancer can be induced in animal models by damaging specific genes.
Introduction of normal copies of damaged genes can reverse a cancer phenotype in cell culture systems.
Most genetic events causing cancer occur in somatic cells.
Frequency of these events can be altered by exposure to mutagens, linking them to environmental carcinogens.

Genetic alterations in cell regulatory systems are the primary basis of carcinogenesis.
Environmental factors interact with genes to contribute to cancer risk.
Different populations exhibit varying cancer frequencies, suggesting environmental and genetic influences.
Both genetics and environment contribute to cancer risk, with interactions between the two.

Genetic control of cell growth and differentiation:
- Growth factors
- Specific receptors for growth factors
- Signal transduction molecules
- Nuclear transcription factors
Mutations can occur in any of the steps involved in regulation of cell growth and differentiation.

The two-hit theory of carcinogenesis states that a cell can initiate a tumor only when it contains two damaged alleles.
A person who inherits one copy of a mutant gene must experience a second, somatic mutation in one or more of that gene in order to develop cancer.

1. Tumor Suppressor Genes:
- Inhibit cellular proliferation
- Act as "brakes" on cell division and proliferation
- Help maintain normal function and integrity of cells
1. Oncogenes (Cancer Genes):
- Most oncogenes originate from proto-oncogenes
- Develop from mutations in any of the four basic regulators of normal cell growth
- A single copy of a mutated oncogene is required to contribute to the multistep process of tumor progression
1. DNA Repair Genes, Chromosome Integrity, and Tumorigenesis:
- Tumor cells typically have widespread mutations, chromosome breaks, and aneuploidy (genomic instability)
- Genomic instability can occur due to defects in proteins required for accurate cell division or in proteins responsible for DNA repair