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Questions and Answers
What type of tumor is associated with the risk of medulloblastoma?
What type of tumor is associated with the risk of medulloblastoma?
What syndrome is caused by a loss-of-function mutation in the STK11 (LKB1) gene?
What syndrome is caused by a loss-of-function mutation in the STK11 (LKB1) gene?
Which apoptotic factor is most commonly inhibited in cancers?
Which apoptotic factor is most commonly inhibited in cancers?
What is a critical factor for the immortality of cancer cells?
What is a critical factor for the immortality of cancer cells?
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What biological process is indicated by telomere shortening during cell division?
What biological process is indicated by telomere shortening during cell division?
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How do tumors with increased glucose metabolism relate to imaging techniques?
How do tumors with increased glucose metabolism relate to imaging techniques?
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What is suggested by the presence of telomerase activity in cancer cells?
What is suggested by the presence of telomerase activity in cancer cells?
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What is the minimum tumor size that typically requires blood supply for its growth?
What is the minimum tumor size that typically requires blood supply for its growth?
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What effect does a mutation in APC have on tumor cells?
What effect does a mutation in APC have on tumor cells?
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Which tumor suppressor gene is associated with benign bilateral schwannomas?
Which tumor suppressor gene is associated with benign bilateral schwannomas?
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Which of the following is a characteristic feature of carcinomas related to E-cadherin mutation?
Which of the following is a characteristic feature of carcinomas related to E-cadherin mutation?
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What is the role of PTCH1 in tumor suppression?
What is the role of PTCH1 in tumor suppression?
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What results from reduced expression of E-cadherin in cancer cells?
What results from reduced expression of E-cadherin in cancer cells?
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What is a consequence of a loss-of-function mutation in E-cadherin?
What is a consequence of a loss-of-function mutation in E-cadherin?
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Which tumor is associated with a mutation on chromosome 11p13?
Which tumor is associated with a mutation on chromosome 11p13?
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What syndrome is caused by germline loss-of-function mutations in PTCH1?
What syndrome is caused by germline loss-of-function mutations in PTCH1?
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What type of mutation in tumor suppressor genes is sufficient to allow tumor proliferation?
What type of mutation in tumor suppressor genes is sufficient to allow tumor proliferation?
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How do loss-of-function mutations in DNA repair genes contribute to cancer development?
How do loss-of-function mutations in DNA repair genes contribute to cancer development?
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Which process allows tumor cells to proliferate without external growth signals?
Which process allows tumor cells to proliferate without external growth signals?
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What is characterized by the switch to aerobic glycolysis in cancer cells?
What is characterized by the switch to aerobic glycolysis in cancer cells?
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What type of mutations in the PIK3 gene are commonly associated with breast carcinomas?
What type of mutations in the PIK3 gene are commonly associated with breast carcinomas?
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Which of the following oncogenes is tightly regulated and involved in immediate early response genes?
Which of the following oncogenes is tightly regulated and involved in immediate early response genes?
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What is the primary consequence of apoptosis-regulating gene mutations in cancer cells?
What is the primary consequence of apoptosis-regulating gene mutations in cancer cells?
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What characteristic of cancer is associated with the ability to invade and metastasize?
What characteristic of cancer is associated with the ability to invade and metastasize?
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What is the consequence of MYC translocation in the context of cancer?
What is the consequence of MYC translocation in the context of cancer?
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Which of the following is NOT a hallmark of cancer?
Which of the following is NOT a hallmark of cancer?
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What type of genetic alteration is responsible for creating a constitutively active BCR-ABL tyrosine kinase?
What type of genetic alteration is responsible for creating a constitutively active BCR-ABL tyrosine kinase?
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In which type of cancer is loss-of-function of the PTEN suppressor gene commonly observed?
In which type of cancer is loss-of-function of the PTEN suppressor gene commonly observed?
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What phenomenon is described as mutations accumulating in a stepwise fashion over time leading to cancer?
What phenomenon is described as mutations accumulating in a stepwise fashion over time leading to cancer?
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What is a primary function of the MYC oncogene?
What is a primary function of the MYC oncogene?
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What type of genetic abnormality is linked to NMYC amplification in cancer?
What type of genetic abnormality is linked to NMYC amplification in cancer?
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Which treatment is commonly used for Chronic Myelogenous Leukemia (CML) due to its efficacy in inhibiting the BCR-ABL kinase?
Which treatment is commonly used for Chronic Myelogenous Leukemia (CML) due to its efficacy in inhibiting the BCR-ABL kinase?
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What is the primary factor stabilizing HIF1α under conditions of low oxygen?
What is the primary factor stabilizing HIF1α under conditions of low oxygen?
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Which factor is NOT typically associated with the promotion of angiogenesis in tumors?
Which factor is NOT typically associated with the promotion of angiogenesis in tumors?
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What mechanism directly contributes to the abnormal vasculature seen in tumors?
What mechanism directly contributes to the abnormal vasculature seen in tumors?
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Which growth factor is typically associated with the increase of ligands that activate the Notch signaling pathway in angiogenesis?
Which growth factor is typically associated with the increase of ligands that activate the Notch signaling pathway in angiogenesis?
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What role do matrix metalloproteinases (MMPs) play in cancer progression?
What role do matrix metalloproteinases (MMPs) play in cancer progression?
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What is the primary consequence of the increased growth factor secretion in angiogenic tumors?
What is the primary consequence of the increased growth factor secretion in angiogenic tumors?
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In the context of cancer metabolism, what characterizes the Warburg effect?
In the context of cancer metabolism, what characterizes the Warburg effect?
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What cellular change is indicated by the downregulation of E-cadherins in the metastatic cascade?
What cellular change is indicated by the downregulation of E-cadherins in the metastatic cascade?
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Study Notes
Tumor Suppressor Genes
- Tumor suppressor genes (TSGs) prevent uncontrolled cell growth and division.
- Loss-of-function mutations in TSGs allow cells to proliferate without any control.
- In most cases, both alleles of the tumor suppressor gene need to be mutated before cancer occurs.
- Haploinsufficiency refers to a condition where a single allele mutation in the TSG is sufficient to allow tumor proliferation.
- Apoptosis-regulating genes can acquire mutations that either increase or decrease cell death, ultimately impacting cancer progression.
- Loss-of-function mutations in DNA repair genes contribute to cancer by impairing the cell's ability to fix DNA damage, resulting in increased mutations and genomic instability.
Hallmarks of Cancer
- Cancer cells exhibit various hallmarks, characteristics that distinguish them from normal cells.
- Self-sufficiency in growth signals: Tumor cells possess the ability to proliferate without any external stimuli due to oncogene activation.
- Insensitivity to growth inhibitory signals: Cancer cells can bypass normal cell cycle checkpoints and continue dividing even in the presence of inhibitory signals.
- Altered cellular metabolism: Cancer cells often switch to aerobic glycolysis, known as the Warburg effect, to generate energy and macromolecules.
- Evasion of apoptosis: Cancer cells acquire mutations that allow them to evade programmed cell death, ensuring their survival and further proliferation.
- Limitless replicative potential: Cancer cells become immortal due to their ability to bypass replicative senescence and overcome the Hayflick limit.
- Sustained angiogenesis: Cancer cells induce the formation of new blood vessels (angiogenesis) to provide oxygen and nutrients, and facilitate tumor growth.
- Ability to invade and metastasize: Cancer cells can invade surrounding tissues and spread to distant locations through metastasis.
MYC Oncogene
- MYC proto-oncogene is a key regulator of cell growth and proliferation.
- It is tightly regulated under normal conditions.
- MYC is involved in various types of cancer, including Burkitt's lymphoma, neuroblastoma, and other B and T cell tumors.
- MYC mutations, such as translocations and amplifications, can lead to uncontrolled cell growth and cancer development.
RAS
- RAS is a proto-oncogene involved in intracellular signaling pathways.
- Loss-of-function mutations in RAS can cause it to be trapped in an active, signaling state, leading to continuous cell proliferation.
PI3K and PTEN
- PI3K is a key signaling pathway involved in cell growth, survival, and metabolism.
- Mutations in PI3K, particularly gain-of-function mutations, are found in a significant percentage of cancers.
- PTEN is a tumor suppressor gene that counteracts the activity of PI3K.
- Loss-of-function mutations in PTEN contribute to cancer development.
E-Cadherin
- E-cadherin is a cell adhesion protein that helps maintain cell-cell junctions.
- Mutations in E-cadherin can lead to loss of contact inhibition, allowing cells to detach from each other.
- This detachment facilitates tumor cell invasion and metastasis.
- Reduced E-cadherin expression is observed in various types of carcinomas.
- Germline loss-of-function mutations in the E-cadherin gene can cause familial gastric carcinoma.
NF2 (Neurofibromatosis Type 2)
- NF2 is a tumor suppressor gene involved in the regulation of cell growth and adhesion.
- Germline mutations in NF2 predispose individuals to neurofibromatosis type 2.
- Somatic mutations in NF2 are observed in sporadic meningiomas and ependymomas.
- Neurofibromin 2 (Merlin), the protein product of NF2, is responsible for maintaining cell-cell junctions and regulating cell growth.
APC
- APC is a tumor suppressor gene involved in the Wnt signaling pathway, regulating cell proliferation and differentiation.
- Mutations in APC can lead to the uncontrolled accumulation of β-catenin in the nucleus, promoting cell division.
- Somatic mutations in APC are found in familial adenomatous polyposis (FAP) and sporadic colorectal cancer.
PATCHED
- PTCH1 is a tumor suppressor gene that encodes a protein called PATCHED1, which regulates the Hedgehog signaling pathway.
- Mutations in PTCH1 can lead to the overactivation of Hedgehog signaling, promoting cell proliferation and tumor growth.
- Germline mutations in PTCH1 cause Gorlin's Syndrome, also known as nevoid basal cell carcinoma syndrome.
VHL (Von Hippel-Lindau)
- VHL is a tumor suppressor gene involved in the regulation of oxygen sensing and angiogenesis.
- Mutations in VHL can lead to the uncontrolled growth of blood vessels, promoting tumor development.
- Germline mutations in VHL are associated with Von Hippel-Lindau syndrome, a multi-organ disorder characterized by various tumors.
STK11 (LKB1)
- STK11 is a tumor suppressor gene that encodes a serine/threonine kinase, playing a role in cellular metabolism and growth regulation.
- Mutations in STK11 can lead to the development of Peutz-Jeghers syndrome, characterized by benign polyps in the gastrointestinal tract.
WARBURG EFFECT
- The Warburg effect is a metabolic hallmark of cancer cells, characterized by increased glucose uptake and aerobic glycolysis.
- Cancer cells rely on glucose fermentation to produce ATP and generate biomass.
- Elevated glucose uptake in cancer cells allows them to be visualized using positron emission tomography (PET) scans.
EVASION OF APOPTOSIS
- Cancer cells often evade apoptosis, or programmed cell death, to survive and proliferate.
- This evasion can occur through various mechanisms, including reduced levels of Fas/CD95, inactivation of caspase 8, upregulation of anti-apoptotic factors (BCL-2, BCL-XL, MCL-1), loss of P53, and upregulation of inhibitors of apoptosis (IAPs).
LIMITLESS REPLICATIVE POTENTIAL
- Cancer cells exhibit limitless replicative potential, due to their ability to bypass the Hayflick limit and overcome senescence.
- Cancer cells often express telomerase, an enzyme that maintains telomere length, preventing the shortening of telomeres associated with cell division and senescence.
SUSTAINED ANGIOGENESIS
- As tumors grow, they require a constant supply of oxygen and nutrients, which necessitates angiogenesis, the formation of new blood vessels.
- The angiogenic switch refers to the transition from a dormant state to an angiogenic state, often driven by hypoxia.
- This switch results in the activation of pro-angiogenic factors, such as VEGF and FGF, and the repression of angiogenesis inhibitors.
INVASION
- Invasion is a crucial step in the metastasis of cancer cells.
- To invade, tumor cells must detach from their surrounding cells, degrade the extracellular matrix, and migrate through tissues.
- The loss of cell-cell adhesion, driven by factors such as decreased E-cadherin expression and secretion of proteolytic enzymes, facilitates invasion.
- Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that break down the extracellular matrix, allowing cancer cells to penetrate surrounding tissues.
METASTASIS
- Metastasis is the spread of cancer cells from the primary tumor site to distant locations.
- The metastatic cascade encompasses a series of steps, including invasion, intravasation, circulation, extravasation, and colonization.
- Metastasis is a complex process involving various cellular and molecular events, and the specific steps and mechanisms can vary among cancer types.
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Description
This quiz covers the role of tumor suppressor genes in cancer biology, detailing how their mutations contribute to uncontrolled cell proliferation. Explore the differences between haploinsufficiency and loss-of-function mutations, along with their implications for cancer progression and genomic stability.