TUMOR SUPPRESSOR GENES & CELL CYCLE CONTROL MCQs | MCQ Quiz | OmpathStudy Kenya

Question 1

What is the chromosomal location of the RB gene?

Accepted Answer

13q14 — The RB gene, the first tumor suppressor gene to be discovered, is located at chromosomal locus 13q14.

Question 2

According to Knudson's two-hit hypothesis, how many mutations are required to develop retinoblastoma?

Accepted Answer

Two hits (mutations) are required — Knudson's two-hit hypothesis states that two hits are required to develop retinoblastoma - both copies of the RB tumor suppressor gene must be dysfunctional.

Question 3

In familial retinoblastoma, what is the origin of the first hit?

Accepted Answer

One mutation is inherited (germline), second is somatic — In familial cases, one hit (mutation) is inherited in the germline and the second hit develops when the normal Rb gene is lost by somatic mutation in retinoblasts.

Question 4

What is the critical cell cycle checkpoint controlled by the RB gene?

Accepted Answer

G1/S transition — The Rb gene exerts antiproliferative effects by controlling the G1/S transition of the cell cycle, preventing cells from entering S phase inappropriately.

Question 5

In its active tumor suppressor form, what is the phosphorylation state of RB protein?

Accepted Answer

Hypophosphorylated — In its active form, Rb is hypophosphorylated and binds to E2F transcription factor, preventing transcription of genes required for DNA replication like cyclin E.

Question 6

What transcription factor does hypophosphorylated RB bind to?

Accepted Answer

E2F — Hypophosphorylated Rb binds to E2F transcription factor, preventing E2F from activating transcription of genes required for cell cycle progression and DNA replication.

Question 7

What percentage of tumors demonstrate biallelic loss of TP53?

Accepted Answer

70% — Approximately 70% of tumors demonstrate biallelic loss of TP53, highlighting its critical role as a tumor suppressor and "guardian of the genome."

Question 8

Which syndrome is associated with germline mutation in one TP53 allele?

Accepted Answer

Li-Fraumeni syndrome — Li-Fraumeni syndrome involves inheritance of one defective TP53 allele in the germline, with the second defect occurring in somatic cells, predisposing to multiple cancers.

Question 9

What is p53 commonly referred to as due to its critical role in genomic stability?

Accepted Answer

Guardian of the genome — p53 is called the "guardian of the genome" because it serves as the central monitor of cellular stress and can initiate responses to maintain genomic integrity.

Question 10

Which stresses can activate p53 protein?

Accepted Answer

Anoxia, oncogene signaling, and DNA damage — p53 is the central monitor of stress in the cell and can be activated by anoxia, inappropriate oncogene signaling, or DNA damage.

Question 11

What mechanism activates p53 in response to DNA damage?

Accepted Answer

Phosphorylation — DNA damage leads to activation of p53 by phosphorylation, which stabilizes the protein and activates its transcriptional functions.

Question 12

What gene does activated p53 drive transcription of to cause G1-S cell cycle block?

Accepted Answer

CDKN1A (p21) — Activated p53 drives transcription of CDKN1A (which encodes p21), a CDK inhibitor that prevents Rb phosphorylation, thereby causing a G1-S block in the cell cycle.

Question 13

What is the purpose of the G1-S cell cycle block induced by p53?

Accepted Answer

To allow cells to repair DNA damage — The pause in cell cycle progression allows cells time to repair DNA damage. If damage cannot be repaired, p53 then induces cellular senescence or apoptosis.

Question 14

If DNA damage cannot be repaired, what outcomes can p53 induce?

Accepted Answer

Cellular senescence or apoptosis — If DNA damage cannot be repaired despite the cell cycle pause, p53 induces either cellular senescence (permanent growth arrest) or apoptosis (programmed cell death).

Question 15

How do oncogenic DNA viruses like HPV disable RB and p53 function?

Accepted Answer

By encoding proteins that bind to RB and p53 — Oncogenic DNA viruses like HPV encode proteins that bind to RB and p53, rendering them non-functional and allowing uncontrolled cell proliferation.

Question 16

What percentage of pancreatic cancers have mutations in at least one component of the TGF-β pathway?

Accepted Answer

100% — In 100% of pancreatic cancers and 83% of colon cancers, at least one component of the TGF-β pathway is mutated, highlighting its critical role as a growth inhibitor.

Question 17

In most normal epithelial, endothelial, and hematopoietic cells, what is the effect of TGF-β?

Accepted Answer

Potent inhibitor of proliferation — In most normal epithelial, endothelial, and hematopoietic cells, TGF-β is a potent inhibitor of proliferation, transmitting antiproliferative signals.

Question 18

What cellular process does TGF-β activate in late-stage tumors that promotes metastasis?

Accepted Answer

Epithelial-to-mesenchymal transition (EMT) — In late-stage tumors, TGF-β signaling can paradoxically activate epithelial-to-mesenchymal transition (EMT), promoting migration, invasion, and metastasis.

Question 19

What does TGF-β signaling activate that has growth-suppressing activity?

Accepted Answer

CDK inhibitors (CDKIs) — TGF-β signaling leads to transcriptional activation of CDK inhibitors (CDKIs) with growth-suppressing activity, while also repressing growth-promoting genes like MYC and cyclins.

Question 20

Which genes does TGF-β signaling repress?

Accepted Answer

MYC, CDK2, CDK4, and cyclins A and E — TGF-β signaling represses growth-promoting genes such as MYC, CDK2, CDK4, and those encoding cyclins A and E, contributing to its antiproliferative effects.

Question 21

What cellular behavior is abolished in cancer cells, allowing them to pile on top of one another?

Accepted Answer

Contact inhibition — Contact inhibition is abolished in cancer cells, allowing them to pile on top of one another and continue proliferating despite cell-cell contact.

Question 22

Which molecule maintains contact inhibition and is lost in malignant cells?

Accepted Answer

E-cadherin — E-cadherin maintains contact inhibition, which is lost in malignant cells, allowing them to overcome this normal growth-limiting mechanism.

Question 23

What protein does the NF2 tumor suppressor gene produce?

Accepted Answer

Neurofibromin-2 (merlin) — The NF2 tumor suppressor gene produces neurofibromin-2 (merlin), which facilitates E-cadherin-mediated contact inhibition.

Question 24

How does the APC gene exert antiproliferative actions?

Accepted Answer

By regulating destruction of cytoplasmic β-catenin — The APC gene exerts antiproliferative actions by regulating the destruction of cytoplasmic β-catenin, preventing its nuclear translocation and transcriptional activity.

Question 25

What happens when APC is mutated and lost?

Accepted Answer

β-catenin accumulates, translocates to nucleus, acts as growth-promoting transcription factor — With APC mutation and loss, β-catenin is not destroyed, accumulates in the cytoplasm, translocates to the nucleus, and acts as a growth-promoting transcription factor.

Question 26

What syndrome is associated with germline mutation of the APC gene?

Accepted Answer

Familial adenomatous polyposis — Familial adenomatous polyposis syndrome involves inheritance of a germline mutation in the APC gene, with sporadic loss of the normal allele causing development of hundreds of colonic polyps at a young age.

Question 27

What percentage of sporadic colon cancers show somatic loss of both APC alleles?

Accepted Answer

70% — Somatic loss of both alleles of the APC gene is seen in approximately 70% of sporadic colon cancers, demonstrating its importance in colorectal carcinogenesis.

Question 28

What are the two main pathways that can initiate apoptosis?

Accepted Answer

Intrinsic and extrinsic pathways — Apoptosis can be initiated through extrinsic (death receptor) or intrinsic (mitochondrial) pathways, both resulting in activation of a proteolytic caspase cascade.

Question 29

What regulates mitochondrial outer membrane permeabilization in apoptosis?

Accepted Answer

Balance between pro-apoptotic (BAX, BAK) and anti-apoptotic molecules (BCL2, BCL-XL) — Mitochondrial outer membrane permeabilization is regulated by the balance between pro-apoptotic molecules (e.g., BAX, BAK) and anti-apoptotic molecules (BCL2, BCL-XL).

Question 30

What is the role of BH3-only proteins in apoptosis?

Accepted Answer

Regulate balance between pro- and anti-apoptotic BCL2 family members — BH3-only proteins (BAD, BID, and PUMA) regulate the balance between pro- and anti-apoptotic members of the BCL2 family, tilting it in favor of pro-apoptotic molecules to activate apoptosis.

Question 31

How do BH3-only molecules activate apoptosis?

Accepted Answer

By tilting balance in favor of pro-apoptotic molecules — BH3-only molecules activate apoptosis by tilting the balance in favor of the pro-apoptotic molecules, promoting mitochondrial outer membrane permeabilization and caspase activation.

Question 32

What is autophagy?

Accepted Answer

Stress-induced process where cells consume their own components — Autophagy is a stress-induced process where cells consume their own components, which cancer cells may avoid through mutations or corrupt to provide parts for continued growth.

Question 33

How can cancer cells manipulate autophagy?

Accepted Answer

Accumulate mutations to avoid it or corrupt it to support growth — Cancer cells may accumulate mutations to avoid autophagy (which could lead to cell death), or may corrupt the process to provide cellular components for continued growth.

Question 34

What happens to telomeres in normal cells with each cell division?

Accepted Answer

They shorten — Telomeres shorten with each cell division in normal cells due to incomplete replication of chromosome ends, eventually activating cell cycle checkpoints leading to senescence.

Question 35

What is the consequence of shortened telomeres in normal cells with intact checkpoints?

Accepted Answer

Senescence — Shortened telomeres in normal cells with intact checkpoints eventually activate cell cycle checkpoints, leading to senescence and placing a limit on the number of divisions.

Question 36

What happens when cells have disabled checkpoints and shortened telomeres?

Accepted Answer

Massive chromosomal instability and mitotic crisis — In cells with disabled checkpoints, DNA repair pathways are inappropriately activated by shortened telomeres, leading to massive chromosomal instability and mitotic crisis.

Question 37

How do tumor cells achieve immortality?

Accepted Answer

By reactivating telomerase — Tumor cells reactivate telomerase, thus staving off mitotic catastrophe from critically shortened telomeres and achieving unlimited replicative potential (immortality).

Question 38

What is the fundamental characteristic of tumor suppressor genes?

Accepted Answer

They apply brakes to cell proliferation — The proteins encoded by tumor suppressor genes apply brakes to cell proliferation. Disruptions of such genes render cells refractory to growth inhibition.

Question 39

How many copies of a tumor suppressor gene must be dysfunctional for tumor development?

Accepted Answer

Both copies must be dysfunctional — Unlike oncogenes (which require only one mutated copy), both copies of a tumor suppressor gene must be dysfunctional for tumor development to occur.

Question 40

What is the clinical consequence of heterozygosity at the RB locus?

Accepted Answer

Not neoplastic — Heterozygosity at the Rb locus (one normal, one mutated allele) is not neoplastic. Both alleles must be lost for tumor development, illustrating the two-hit hypothesis.

Question 41

What cancers besides retinoblastoma show homozygous loss of RB gene?

Accepted Answer

Multiple other cancers — Homozygous loss or mutation of the Rb gene is seen in retinoblastoma and many other cancers, demonstrating its broader role as a tumor suppressor beyond its tissue of discovery.

Question 42

Almost all cancers have a disabled G1 checkpoint due to what?

Accepted Answer

RB mutation or mutations affecting RB function (cyclin D, CDK4, CDKIs) — Almost all cancers have a disabled G1 checkpoint due to either RB mutation or mutations in genes that affect Rb function, such as cyclin D, CDK4, and CDK inhibitors.

Question 43

What is the relationship between TGF-β receptors I and II in signal transduction?

Accepted Answer

They form a complex upon ligand binding — TGF-β regulates cellular processes by binding to a complex composed of TGF-β receptors I and II. Dimerization of the receptors upon ligand binding initiates the signaling cascade.

Question 44

In sporadic retinoblastoma, what is the origin of both hits?

Accepted Answer

Both are somatic mutations in one retinoblast — In sporadic cases, both normal RB alleles are lost by somatic mutation in one retinoblast, requiring two independent mutational events in the same cell.

Question 45

What members of the BCL2 family are pro-apoptotic?

Accepted Answer

BAX and BAK — BAX and BAK are pro-apoptotic members of the BCL2 family that promote mitochondrial outer membrane permeabilization, while BCL2 and BCL-XL are anti-apoptotic.

Question 46

What members of the BCL2 family are anti-apoptotic?

Accepted Answer

BCL2 and BCL-XL — BCL2 and BCL-XL are anti-apoptotic molecules that prevent mitochondrial outer membrane permeabilization and inhibit apoptosis, opposing the actions of BAX and BAK.

Question 47

What inevitably happens to polyps in familial adenomatous polyposis?

Accepted Answer

One or more evolve into colonic cancer — In familial adenomatous polyposis, patients develop hundreds of colonic polyps at a young age, and inevitably one or more of these polyps evolve into colonic cancer.

Question 48

Which genes does activated p53 control in response to stress?

Accepted Answer

Genes involved in cell cycle arrest, DNA repair, senescence, and apoptosis — Activated p53 controls the expression and activity of genes involved in multiple protective responses: cell cycle arrest, DNA repair, cellular senescence, and apoptosis.

Question 49

What is the functional consequence of RB binding to E2F?

Accepted Answer

Prevention of transcription of genes required for DNA replication — When hypophosphorylated Rb binds to E2F transcription factor, it prevents E2F from activating transcription of genes required for DNA replication, such as cyclin E, thus blocking cell cycle progression.

Question 50

What fundamental process in carcinogenesis involves failure of growth inhibition?

Accepted Answer

Insensitivity to growth inhibitory signals — Failure of growth inhibition (insensitivity to growth inhibitory signals) is fundamental in carcinogenesis. Disruption of tumor suppressor genes renders cells refractory to growth inhibition and mimics growth-promoting effects.

TUMOR SUPPRESSOR GENES & CELL CYCLE CONTROL MCQs | MCQ Quiz | OmpathStudy Kenya

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