Lecture 21

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Questions and Answers

What is the result of a balanced translocation in tumor cells?

Loss of a whole chromosome

Amplification of a particular gene

Exchange of segments between two chromosomes (correct)

Deletion of a segment of a chromosome

What type of chromosomal abnormality is commonly seen in solid tumors?

Gene amplification

Deletion of a segment of a chromosome (correct)

Aneuploidy

Balanced translocation

Which of the following genes is amplified in neuroblastoma?

HER-2

BCR-ABL

RET

N-MYC (correct)

What is the term for a chromosome number that is not a multiple of 23 in humans?

Aneuploidy Signup and view all the answers

What is the function of BCL-2 in apoptosis?

To maintain the balance between pro-apoptotic and anti-apoptotic molecules Signup and view all the answers

What is the result of gene amplification in tumor cells?

Increased production of a particular gene Signup and view all the answers

What is required for the development of cancer?

The accumulation of multiple mutations Signup and view all the answers

Which gene is responsible for protecting tumor cells from apoptosis in follicular lymphoma?

BCL-2 Signup and view all the answers

What is the role of TP53 in apoptosis?

It induces apoptosis in cells with irreparable DNA damage Signup and view all the answers

What is the first step in the process of invasion and metastasis?

Detachment of tumor cells from each other Signup and view all the answers

What is the function of proteolytic enzymes in invasion and metastasis?

They degrade the extracellular matrix Signup and view all the answers

What determines the metastatic site of a tumor?

The location of the primary tumor and its vascular and lymphatic drainage Signup and view all the answers

What is the role of vascularization in tumor growth and metastasis?

It is essential for tumor growth and metastasis Signup and view all the answers

What is organ tropism in the context of metastasis?

The ability of tumor cells to migrate to specific organs Signup and view all the answers

What is the primary reason individuals with inherited defects in DNA repair genes are at greater risk for cancer development?

Because of their inability to repair DNA damage Signup and view all the answers

What is the outcome of environmental hazards causing DNA damage in normal cells?

Repair of DNA damage Signup and view all the answers

What is the result of the failure to repair DNA damage in cells?

Genomic instability Signup and view all the answers

What is the characteristic of tumor cells that are more adept at evading host defenses?

Increased aggression Signup and view all the answers

What is the role of BRCA1 and BRCA2 in familial breast cancers?

Involvement in DNA repair Signup and view all the answers

What is the result of clonal expansion of tumor cells?

Progression to malignancy Signup and view all the answers

What is the characteristic of hereditary nonpolyposis colon cancer syndrome (HNPCC)?

Defective DNA repair Signup and view all the answers

What is the outcome of genetic damage during carcinogenesis?

Small genetic damage Signup and view all the answers

What is the role of VEGF in tumor cells?

Promoting angiogenesis Signup and view all the answers

What is the function of HIF in response to hypoxia?

Activating VEGF transcription Signup and view all the answers

What is the role of the VHL gene in tumor suppression?

Inhibiting HIF Signup and view all the answers

What is the reason for cellular senescence after 60-70 cell doublings?

Progressive shortening of telomeres Signup and view all the answers

What is the effect of P53 and RB mutations on cellular senescence?

Cells cannot recognize DNA damage and keep dividing Signup and view all the answers

What is the role of telomerase in cancer cells?

Reacting telomere segments in chromosomes Signup and view all the answers

What is the result of multiple mutations in different cells during tumor progression?

Generation of heterogenous cells with different characteristics Signup and view all the answers

What is the significance of VEGF antibody in cancer treatment?

It is now approved for treatment of some cancer Signup and view all the answers

Study Notes

Resisting Cell Death (Apoptosis)

BCL-2 controls apoptosis by balancing pro-apoptotic (BAX, BAK) and anti-apoptotic molecules
Apoptosis can be activated by intrinsic (mitochondrial) and extrinsic pathways, leading to caspase activation
Mitochondrial membrane permeability is regulated by BCL2
In 85% of follicular lymphoma cases, the anti-apoptotic BCL2 gene protects tumor cells from apoptosis
TP53 is a pro-apoptotic gene that induces apoptosis in cells with irreparable DNA damage

Activating Invasion and Metastasis

Divided into three steps: invasion of extracellular matrix, vascular dissemination, and homing of tumor cells
Invasion involves detachment of tumor cells from each other, degradation of basement membrane and interstitial matrix, and attachment to new binding sites
Vascular dissemination and homing of tumor cells involve adhesion to vascular endothelium and entrance into other organ parenchyma
Metastatic site prediction is influenced by primary tumor location and vascular and lymphatic drainage
Organ tropism is exhibited by some tumors, possibly due to activation of adhesion or chemokine receptors

Inducing Angiogenesis

Vascularization of tumor cells is essential for growth and metastasis
Hypoxia activates HIF1α, leading to transcription of VEGF genes and subsequent angiogenesis
VEGF secreted by tumor cells leads to new vessel formation
HIF1α is inactivated by VHL gene (tumor suppressor gene)
VEGF antibody is approved for treatment of some cancers

Enabling Replicative Immortality

Cells lose capacity to divide and enter senescence after 60-70 cell doublings due to telomere shortening
Short telomeres are recognized as DNA damage, leading to cell cycle arrest mediated by P53 and RB
Cancer cells can reactivate telomerase, achieving immortality
Cells with mutation in P53 and RB genes cannot recognize DNA damage and continue to divide

The Molecular Basis of Cancer

Carcinogenesis is a multistep process resulting from multiple genetic alterations
Tumor progression and heterogeneity result from multiple mutations accumulating independently in different cells
New subclones arise from the descendants of the original transformed cell by multiple mutations
Environmental hazards, inherited mutations, and DNA damage contribute to carcinogenesis

Genomic Instability

Normal cells are able to repair DNA damage
Individuals with inherited defects in DNA repair genes are at greater risk for cancer development
Examples include Hereditary non-polyposis colon cancer syndrome, Xeroderma pigmentosum, and BRCA1 and BRCA2 in familial breast cancers

Karyotopic Changes in Tumors

Genetic damage during carcinogenesis can result in small (point mutations) or large chromosomal changes
Common types of structural abnormalities in tumor cells include balanced translocations, deletions, gene amplification, and aneuploidy
Examples of balanced translocations include the Philadelphia (Ph) chromosome in chronic myelogenous leukemia and t(8;14) in Burkitt’s leukemia/lymphoma

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Description

This quiz covers the hallmarks of cancer, specifically resisting cell death through apoptosis. Learn about the roles of BCL-2, BAX, and BAK in regulating apoptosis and mitochondrial membrane permeability.