FOM- week 9 Flashcards
What is cancer?
Cancer is uncontrolled cell growth that invades other tissues and can spread to distant organs.
What are tumors?
Tumors are swellings that can be benign (non-cancerous) or malignant (cancerous).
What is neoplasia?
Neoplasia is abnormal, uncontrolled growth of cells without a stimulus. It can be benign, premalignant, or malignant.
What is metaplasia?
Metaplasia is a reversible change in cell type, often due to stress (e.g., smoking).
What is dysplasia?
Dysplasia is abnormal cell growth that may lead to cancer.
What is malignancy?
Malignant cells invade surrounding tissues and can metastasize (spread) to distant sites.
What are the hallmarks of cancer?
- Evading growth suppression
- Avoiding immune destruction
- Sustaining proliferative signals
- Inducing angiogenesis
- Genome instability (mutations)
What are oncogenes?
Oncogenes (e.g., MYc, BRAF, RAS) promote cancer by accelerating the cell cycle.
What are tumor suppressor genes?
Tumor suppressor genes (e.g., p53) inhibit cell cycle progression and promote apoptosis. Loss of these genes can lead to cancer.
What causes cancer?
Cancer is a genetic disease arising from somatic cell mutations, driven by mosaicism and post-zygotic mutations, leading to a genetically diverse population of cells within an individual.
What are somatic mutations?
Somatic mutations occur in non-reproductive cells and cannot be inherited.
What is mosaicism?
Mosaicism refers to the presence of multiple genetically distinct cell lines within an individual due to mutations occurring during development.
What are driver mutations vs passenger mutations?
Driver mutations drive cancer development by altering critical genes (oncogenes and tumor suppressors). Passenger mutations are incidental and do not directly cause cancer.
What is epigenetics and its role in cancer?
Epigenetic changes alter gene expression without changing the DNA sequence, potentially turning genes on or off, contributing to cancer.
What is DNA methylation?
DNA methylation involves adding a methyl group to DNA, usually silencing gene expression. In cancer, tumor suppressor genes may be hypermethylated and silenced.
What is histone modification?
Histone modifications affect the proteins around which DNA is wrapped, influencing gene expression and potentially contributing to cancer.
What is methylation in cancer?
Methylation typically occurs at CpG sites, and hypermethylation of tumor suppressor genes can silence these genes, contributing to cancer development.
What are oncogenes?
Oncogenes are mutated or overexpressed proto-oncogenes that promote cancer cell growth. They can produce their own growth factors, overexpress receptors, or have constitutively active proteins.
How are oncogenes activated?
Oncogenes can be activated through: Point mutations (e.g., BRAF), Amplification (e.g., HER2), Translocation (e.g., Philadelphia Chromosome BCR-ABL).
What is the role of the BRAF gene in cancer?
A point mutation in the BRAF gene causes constitutive activation of the MAP-Kinase signaling pathway, leading to constant cell growth signals.
What is HER2 amplification?
HER2 gene amplification results in excessive HER2 receptors on the cell surface, promoting uncontrolled cell proliferation.
What is the Philadelphia Chromosome?
A translocation between chromosomes 9 and 22 creates a BCR-ABL fusion protein, which has enhanced kinase activity, promoting cancer cell growth.
What is the role of tumor suppressor genes?
Tumor suppressor genes inhibit cancerous growth by regulating the cell cycle and initiating apoptosis. Mutations in these genes can lead to cancer.
What is the RB gene and its role in cancer?
The RB gene encodes pRB, a protein that controls the G1 checkpoint in the cell cycle. Mutations in this gene lead to uncontrolled cell division and retinoblastoma.
What is the Two-Hit Hypothesis?
The Two-Hit Hypothesis suggests that both alleles of a tumor suppressor gene must be mutated or deleted for cancer to develop. This explains cancer’s increasing frequency with age.
What is mismatch repair and its role in cancer?
Mismatch repair fixes DNA replication errors. Failure in this system (e.g., in Lynch Syndrome) leads to an increased mutation rate and higher cancer risk.
What is Lynch Syndrome?
Lynch Syndrome is a hereditary form of colon cancer caused by mutations in mismatch repair genes, leading to failure in correcting replication errors.
What is an oncogenic signature?
Cancer cells exhibit an oncogenic signature, a combination of driver mutations that define the cancer and contribute to tumor heterogeneity and rapid evolution.
What causes cancer?
Cancer is a genetic disease that arises from somatic mutations and mosaicism, caused by post-zygotic mutations that result in genetically diverse cells.
What are somatic mutations?
Somatic mutations occur in non-reproductive cells and are not inherited.
What is mosaicism?
Mosaicism is the presence of more than one genetically distinct cell line within an individual due to mutations occurring during development.
What are driver mutations vs passenger mutations?
Driver mutations directly contribute to cancer development by altering critical genes, while passenger mutations are incidental and do not cause cancer.
What is epigenetics and its role in cancer?
Epigenetics involves changes in gene expression without altering the DNA sequence. These changes, like DNA methylation, can drive cancer by turning important genes on or off.
What is DNA methylation?
DNA methylation adds a methyl group to DNA, silencing gene expression. Hypermethylation of tumor suppressor genes can contribute to cancer.
What is histone modification?
Histone modification refers to changes in the proteins around which DNA is wrapped, influencing gene expression and potentially driving cancer.
What are oncogenes?
Oncogenes are mutated or overexpressed proto-oncogenes that drive cancer cell growth by producing growth factors, overexpressing receptors, or having constitutively active proteins.
How are oncogenes activated?
Oncogenes can be activated by point mutations (e.g., BRAF), gene amplification (e.g., HER2), or chromosomal translocations (e.g., Philadelphia Chromosome BCR-ABL).
What is BRAF’s role in cancer?
A point mutation in BRAF causes constant activation of the MAP-Kinase pathway, promoting cell growth.
What is HER2 amplification?
HER2 gene amplification leads to excessive HER2 receptors on the cell surface, resulting in uncontrolled cell proliferation.
What is the Philadelphia Chromosome?
A translocation between chromosomes 9 and 22 creates a BCR-ABL fusion protein, enhancing kinase activity and promoting uncontrolled cell growth.
What are tumor suppressor genes?
Tumor suppressor genes inhibit cancerous growth by regulating the cell cycle and initiating apoptosis. Mutations in these genes can lead to cancer.
What is the RB gene and its role in cancer?
The RB gene encodes pRB, a protein that prevents uncontrolled cell division at the G1 checkpoint. Mutations cause retinoblastoma and other cancers.
What is the Two-Hit Hypothesis?
The Two-Hit Hypothesis states that both alleles of a tumor suppressor gene must be mutated for cancer to develop, explaining why cancer occurs more frequently with age.
What is mismatch repair and its role in cancer?
Mismatch repair corrects DNA replication errors. Failure in mismatch repair (e.g., Lynch Syndrome) leads to increased mutations and higher cancer risk.
What is Lynch Syndrome?
Lynch Syndrome is a hereditary condition caused by mutations in mismatch repair genes, leading to an increased risk of colon cancer.
What is an oncogenic signature?
An oncogenic signature is a combination of driver mutations that characterize a cancer and contribute to tumor heterogeneity and rapid evolution.
What factors contribute to cancer risk?
Cancer risk is multifactorial, influenced by genetic predisposition, lifestyle factors, and environmental exposures.
What are indicators of inherited cancer susceptibility?
Indicators include multiple affected family members, early onset of cancer, bilateral tumors, and multiple cancers in a single individual.
How is cancer risk multifactorial?
Cancer risk is influenced by a combination of genetic factors and environmental/lifestyle factors, not just by genetics alone.
What is the role of DNA repair in cancer?
DNA repair mechanisms like mismatch repair are critical in preventing cancer. Defects in these systems can lead to increased mutation rates and higher cancer risk.
What is the Warburg Effect?
Cancer cells use anaerobic glycolysis (even in the presence of oxygen) for rapid energy production, supporting fast cell growth but producing inefficient ATP and lactate.
What is glycolysis and where does it occur?
Glycolysis is the process that converts glucose to pyruvate and occurs in the cytoplasm, yielding 2 ATP per glucose molecule.
What is the role of glucose in metabolism?
Glucose is used for ATP production and as a building block for synthetic reactions, such as nucleotide synthesis via the pentose phosphate pathway.
How does glucose enter cells?
Glucose enters cells through Na+/glucose symporters or GLUTs (glucose transporters), regulated by tissue type.
What are the key enzymes in glycolysis?
Key enzymes include hexokinase, phosphofructokinase, aldolase, and pyruvate kinase, which regulate the flow of glucose to pyruvate.
What is the role of phosphofructokinase in glycolysis?
Phosphofructokinase is the rate-limiting enzyme in glycolysis, activated by AMP and inhibited by ATP and citrate.
What happens in anaerobic metabolism?
In the absence of oxygen, pyruvate is converted to lactate, regenerating NAD+ for continued glycolysis.
What is the fate of pyruvate in metabolism?
Pyruvate is converted to acetyl-CoA for the TCA cycle, where it undergoes further oxidation to produce ATP, NADH, and FADH2.
What is the TCA Cycle?
The TCA cycle occurs in the mitochondrial matrix and oxidizes acetyl-CoA to produce ATP, NADH, FADH2, and CO2.
What is the overall ATP yield from glucose metabolism?
One molecule of glucose yields 30-32 ATP through glycolysis, the TCA cycle, and oxidative phosphorylation.
What is oxidative phosphorylation?
Oxidative phosphorylation is the process by which ATP is generated using the electron transport chain and a proton gradient in the inner mitochondrial membrane.
What is the role of NADH and FADH2 in oxidative phosphorylation?
NADH and FADH2 carry high-energy electrons to the electron transport chain, which transfers electrons to oxygen, generating a proton gradient used for ATP synthesis.
What inhibits oxidative phosphorylation?
Cyanide, azide, and CO inhibit electron transfer to O2, preventing the proton gradient formation and halting ATP synthesis.
