oncogenesis exam 3

What is oncogenesis?

The biological process by which normal cells transform into cancer cells due to accumulation of mutations and genetic alterations.

What is cancer?

A heterogeneous group of disorders characterized by uncontrolled cell division, resulting in overgrowth of mutated cells that gain an advantage over normal cells.

What are risk factors for cancer?

Genetic predisposition, environmental exposures (tobacco, diet, obesity, alcohol, ultraviolet radiation, ionizing radiation, pollutants), viral infections, and age due to accumulated mutations.

What is genetic predisposition?

Inherited susceptibility that increases the likelihood of developing malignancy.

What are passenger mutations?

Mutations that occur during tumor development but do not provide a growth advantage to the cancer cells.

What are driver mutations?

Mutations that directly contribute to tumor initiation and progression by providing growth or survival advantages.

What is clonality in cancer?

The principle that all tumor cells are derived from a single original mutated cell.

What is autonomy in cancer cells?

The ability of malignant cells to override normal regulatory growth mechanisms.

What are tumor suppressor genes?

Genes that prevent inappropriate proliferation and repair damaged DNA; both alleles must be lost for cancer to occur.

What is loss of heterozygosity?

The loss of the normal allele when the other allele is already mutated, leading to complete loss of function of a gene.

What is the RB gene?

A tumor suppressor gene; mutation of RB predisposes to retinoblastoma.

What is the TP53 gene?

A tumor suppressor gene encoding the p53 protein, known as the "guardian of the genome."

What is Li-Fraumeni syndrome?

An inherited germline mutation of TP53 leading to greatly increased risk of multiple cancers, including colon, breast, and brain, by age 30.

What are proto-oncogenes?

Normal cellular genes that regulate growth and division, such as growth factors, receptors, intracellular kinases, and transcription factors.

What are oncogenes?

Mutated proto-oncogenes that promote uncontrolled cell division; gain of function mutations lead to cancer.

What mechanisms activate oncogenes?

Promoter or enhancer insertion, gene amplification, point mutations, and chromosomal translocations.

How do viruses cause cancer?

By introducing transforming genes, inserting strong promoters near proto-oncogenes, rearranging host proto-oncogenes, impairing DNA repair, and promoting chronic inflammation.

What regulates the cell cycle?

Cyclins and cyclin-dependent kinases at checkpoints ensure proper progression through G1, S, G2, and M phases.

What is the significance of G1 to S checkpoint mutations?

They are oncogenic and found in approximately 80 percent of human cancers, allowing uncontrolled division.

What is the Ras/MAPK pathway?

A signaling cascade where growth factor binding activates a receptor, adaptor proteins, Ras, a kinase cascade, MAPK, and transcription factors, leading to cell division.

What are DNA repair genes?

Genes that monitor and repair DNA replication errors; their loss leads to reduced replication fidelity and chromosomal rearrangements.

What is telomerase?

An enzyme that elongates chromosome ends (telomeres) to maintain replicative potential, reactivated in 90 percent of tumors.

What is hTERT?

Human telomerase reverse transcriptase, the catalytic subunit of telomerase, often activated by promoter mutations in cancer.

What is apoptosis?

Programmed cell death, a regulated energy-dependent process involving caspase enzymes and triggered by signals such as death receptors, mitochondrial dysfunction, or growth factor deprivation.

How do cancer cells evade apoptosis?

By disabling caspases or enhancing anti-apoptotic survival signals.

What is epigenetics?

Regulation of gene expression without altering the DNA sequence, including DNA methylation and histone modifications.

What is DNA methylation?

Addition of methyl groups to CpG sites in DNA, usually silencing genes; aberrant methylation can silence tumor suppressor genes and promote cancer.

What is angiogenesis?

Formation of new blood vessels to supply tumors; necessary once tumor size exceeds 1 cubic millimeter.

What angiogenic factors are secreted by tumors?

Vascular Endothelial Growth Factor (VEGF), Transforming Growth Factor-beta (TGF-β), basic Fibroblast Growth Factor (bFGF), and Interleukin-8 (IL-8).

What are angiogenesis inhibitors?

Molecules such as interferons that block the formation of new blood vessels.

What is invasion in cancer?

The process by which malignant cells penetrate the basement membrane and enter surrounding stroma, aided by reduced E-cadherin and high matrix metalloproteinases.

What is metastasis?

The spread of malignant cells to distant sites through blood or lymphatic systems, involving intravasation into circulation, survival, extravasation, and colonization of new tissue.