ONCOPATHOLOGY MCQ EXAMINATION HAllmarks of Cancer 1,2 &3 | MCQ Quiz | OmpathStudy Kenya

Question 1

A patient with familial retinoblastoma develops bilateral tumors at age 3. According to Knudson's hypothesis, what distinguishes this presentation from sporadic cases?

Accepted Answer

The first mutation is inherited, requiring only one somatic hit — In familial retinoblastoma, one mutation is inherited (germline), so only one additional somatic mutation is needed. Sporadic cases require both mutations to occur somatically in the same cell.

Question 2

Which event would MOST effectively prevent E2F-mediated transcription of S-phase genes?

Accepted Answer

Hypophosphorylation of RB protein — Hypophosphorylated RB binds to and sequesters E2F, preventing transcription. Hyperphosphorylation releases E2F, allowing transcription to proceed.

Question 3

A tumor shows constitutive activation of growth signaling despite absence of growth factors. Which mechanism is LEAST likely responsible?

Accepted Answer

Loss of p53 function — Loss of p53 primarily affects cell cycle checkpoints and apoptosis, not growth factor signaling. The other options directly cause self-sufficiency in growth signals.

Question 4

In chronic myeloid leukemia, the BCR-ABL fusion protein drives malignancy primarily by

Accepted Answer

Constitutive tyrosine kinase activity without regulation — The BCR-ABL fusion results from t(9;22) translocation and causes loss of the regulatory region controlling tyrosine kinase activity, leading to continuous mitogenic signaling.

Question 5

A researcher observes that tumor cells continue dividing despite contact with neighboring cells. Which protein's function is most likely compromised?

Accepted Answer

E-cadherin — E-cadherin mediates contact inhibition. Its loss allows cancer cells to pile on top of each other and continue dividing despite cell-cell contact.

Question 6

Why must BOTH copies of a tumor suppressor gene be lost for tumor development, unlike oncogenes which require mutation of only one allele?

Accepted Answer

The remaining normal allele can still produce functional protein — This follows Knudson's two-hit hypothesis. One functional copy of a tumor suppressor gene is sufficient for normal function, so both must be lost. Oncogenes are gain-of-function mutations where one mutant copy is sufficient.

Question 7

A tumor expresses high levels of p16INK4a but shows uncontrolled proliferation. Which alteration would explain this paradox?

Accepted Answer

Mutation in CDK4 preventing p16INK4a binding — If CDK4 is mutated such that p16INK4a cannot bind to it, p16INK4a cannot inhibit the cyclin D-CDK4 complex, rendering its overexpression ineffective.

Question 8

Which statement BEST explains why p53 is called the 'guardian of the genome'?

Accepted Answer

It monitors cellular stress and coordinates cell cycle arrest or apoptosis — p53 acts as a central stress monitor that can activate pathways for DNA repair, cell cycle arrest, senescence, or apoptosis depending on the severity of damage. It doesn't repair DNA directly but coordinates the response.

Question 9

In pancreatic cancer, TGF-β pathway mutations are found in 100% of cases. However, in late-stage tumors, intact TGF-β signaling promotes metastasis. This apparent contradiction occurs because

Accepted Answer

TGF-β switches from growth inhibition to promoting EMT and invasion — TGF-β has dual roles: in normal/early cancer cells it inhibits growth, but in late-stage tumors it can activate epithelial-to-mesenchymal transition (EMT), promoting migration and metastasis.

Question 10

A patient with Li-Fraumeni syndrome develops multiple tumors at young age. The inherited defect most likely involves

Accepted Answer

One allele of TP53 gene — Li-Fraumeni syndrome involves germline mutation of one TP53 allele. The second hit occurs somatically, leading to multiple tumor types at young age due to loss of this critical tumor suppressor.

Question 11

During mitosis, which cyclin-CDK complex is responsible for nuclear membrane breakdown?

Accepted Answer

Cyclin B-CDK1 — Cyclin B-CDK1 complex is activated by protein phosphatase at the G2/M transition and causes nuclear membrane breakdown, initiating mitosis.

Question 12

Which scenario would MOST likely result in failed DNA damage repair followed by apoptosis?

Accepted Answer

Normal p53 with irreparable DNA damage — Normal p53 can induce apoptosis when DNA damage is irreparable. Mutated p53 fails to trigger apoptosis even with extensive damage. BCL2 overexpression blocks apoptosis.

Question 13

A tumor shows loss of APC function. What is the immediate downstream effect?

Accepted Answer

Nuclear accumulation of β-catenin acting as transcription factor — APC normally promotes β-catenin degradation. Loss of APC leads to β-catenin accumulation and nuclear translocation, where it acts as a growth-promoting transcription factor.

Question 14

Why do HPV oncoproteins preferentially target both RB and p53 proteins?

Accepted Answer

Inactivating both allows bypass of major cell cycle checkpoints — RB controls the G1/S checkpoint while p53 controls multiple checkpoints and apoptosis. Inactivating both allows the virus to drive cell proliferation while evading protective mechanisms.

Question 15

A researcher finds that tumor cells produce the same growth factor for which they express receptors. This exemplifies which hallmark of cancer?

Accepted Answer

Self-sufficiency in growth signals — Autocrine signaling (producing growth factors for one's own receptors) is a classic mechanism of self-sufficiency in growth signals, eliminating dependence on external growth factors.

Question 16

What is the functional significance of cyclin D appearing in mid-G1 phase?

Accepted Answer

It initiates RB phosphorylation to progress toward S phase — Cyclin D binds CDK4 to form a complex that phosphorylates RB. This is the first critical step in committing the cell to proceed through the restriction point toward S phase.

Question 17

Which mechanism does NOT contribute to the 'angiogenic switch' in tumors?

Accepted Answer

Enhanced E-cadherin expression — E-cadherin is involved in cell-cell adhesion and contact inhibition, not angiogenesis. The other options all promote the angiogenic switch by increasing pro-angiogenic factors or decreasing inhibitors.

Question 18

Patients with xeroderma pigmentosum develop skin cancers primarily because

Accepted Answer

They cannot repair UV-induced pyrimidine dimers — Xeroderma pigmentosum involves defects in nucleotide excision repair, preventing repair of UV-induced pyrimidine dimers in DNA, leading to accumulation of mutations and skin cancer.

Question 19

In von Hippel-Lindau (VHL) syndrome, loss of VHL protein function leads to cancer primarily through

Accepted Answer

Stabilization of HIF-1α and increased VEGF transcription — VHL normally targets HIF-1α for degradation in normoxic conditions. Loss of VHL leads to HIF-1α accumulation, nuclear translocation, and transcription of pro-angiogenic genes like VEGF.

Question 20

The "point of no return" in the cell cycle, after which cells are committed to division, occurs at

Accepted Answer

G1/S transition — The G1/S transition (restriction point) is the critical decision point. Once cells pass this checkpoint, they are committed to completing the cell cycle.

Question 21

A tumor measuring 3 mm in diameter shows areas of necrosis in its center. This observation suggests

Accepted Answer

Failure to induce angiogenesis beyond 1-2 mm diameter — Tumors cannot grow beyond 1-2 mm without angiogenesis due to the limited diffusion distance of oxygen and nutrients. Central necrosis indicates inadequate vascularization.

Question 22

What distinguishes proto-oncogenes from oncogenes?

Accepted Answer

Proto-oncogenes are normal genes; oncogenes are mutated versions — Proto-oncogenes are normal cellular genes that regulate cell proliferation and differentiation. Oncogenes are mutated or overexpressed versions that promote uncontrolled growth.

Question 23

In familial adenomatous polyposis syndrome, hundreds of colonic polyps develop due to

Accepted Answer

Germline mutation in one APC allele plus somatic loss of the second — FAP follows the two-hit hypothesis for tumor suppressors. Patients inherit one mutant APC allele, and sporadic loss of the second allele in individual cells leads to multiple polyps.

Question 24

The Warburg effect refers to cancer cells'

Accepted Answer

Preference for aerobic glycolysis despite oxygen availability — The Warburg effect (aerobic glycolysis) involves cancer cells using glycolysis even when oxygen is available, sacrificing ATP efficiency for rapid biomass production to support proliferation.

Question 25

Which statement about the G2/M checkpoint is correct?

Accepted Answer

It checks completion of DNA replication before mitosis — The G2/M checkpoint ensures DNA replication is complete and checks for DNA damage before allowing the cell to enter mitosis. Defects lead to chromosomal abnormalities.

Question 26

p21, p27, and p57 belong to which family of cell cycle regulators?

Accepted Answer

Cip/Kip family of CDK inhibitors — p21, p27, and p57 are members of the Cip/Kip family of CDK inhibitors that bind and inactivate cyclin-CDK complexes. p21 is transcriptionally activated by p53.

Question 27

Matrix metalloproteinases (MMPs) facilitate tumor invasion by

Accepted Answer

Degrading ECM and releasing sequestered growth factors — MMPs degrade basement membrane and ECM components, facilitating invasion. They also release ECM-bound growth factors like VEGF and generate chemotactic fragments.

Question 28

Why do cancer cells typically show microsatellite instability (MSI) in hereditary nonpolyposis colon cancer (HNPCC)?

Accepted Answer

Defective mismatch repair system — HNPCC patients have mutations in mismatch repair genes, leading to failure to correct replication errors, particularly in repetitive sequences (microsatellites), causing MSI.

Question 29

Tumor cells achieve immortality primarily by

Accepted Answer

Reactivating telomerase to maintain telomere length — Normal cells have limited replicative potential due to telomere shortening. Cancer cells reactivate telomerase to maintain telomeres, achieving unlimited replicative potential.

Question 30

In the multistep carcinogenesis model of colon cancer, which genetic alteration typically occurs FIRST?

Accepted Answer

Inactivation of APC — The adenoma-carcinoma sequence in colon cancer typically begins with APC inactivation, followed by KRAS activation, then loss of 18q tumor suppressors, and finally TP53 loss.

Question 31

BH3-only proteins (BAD, BID, PUMA) regulate apoptosis by

Accepted Answer

Tilting the balance toward pro-apoptotic BCL2 family members — BH3-only proteins regulate the balance between pro-apoptotic (BAX, BAK) and anti-apoptotic (BCL2, BCL-XL) proteins, promoting mitochondrial outer membrane permeabilization when apoptosis is needed.

Question 32

A tumor biopsy shows overexpression of MYC oncogene. What is the primary consequence?

Accepted Answer

Potent transcriptional activation leading to increased proliferation — MYC is a transcription factor commonly involved in human cancers. It drives expression of genes involved in cell growth, proliferation, and metabolism.

Question 33

The term "two-hit hypothesis" specifically applies to

Accepted Answer

Tumor suppressor genes — Knudson's two-hit hypothesis applies to tumor suppressor genes, requiring inactivation of both alleles for loss of function. Oncogenes require only one activating mutation (gain of function).

Question 34

Thrombospondin-1 (TSP-1) functions in tumor biology as

Accepted Answer

An angiogenesis inhibitor — TSP-1 is a potent angiogenesis inhibitor. Normal p53 induces TSP-1 synthesis. Loss of p53 in tumors reduces TSP-1, contributing to the angiogenic switch.

Question 35

What distinguishes benign tumors from malignant tumors regarding angiogenesis?

Accepted Answer

Both require angiogenesis for continued growth beyond 1-2 mm — Both benign and malignant tumors require angiogenesis to grow beyond the diffusion limit of oxygen and nutrients (1-2 mm). However, tumor vessels are typically abnormal and leaky.

Question 36

The primary role of NF2 (neurofibromin-2/merlin) in tumor suppression is

Accepted Answer

Facilitation of E-cadherin-mediated contact inhibition — NF2 produces merlin, which facilitates E-cadherin-mediated contact inhibition. Loss of NF2 contributes to the loss of contact inhibition seen in cancer cells.

Question 37

A PET scan using 18F-fluorodeoxyglucose shows intense uptake in a tumor. This indicates

Accepted Answer

Increased glucose uptake due to Warburg effect — Cancer cells show increased glucose uptake due to aerobic glycolysis (Warburg effect). PET scanning exploits this "glucose hunger" using a non-metabolizable glucose analog.

Question 38

Which scenario best represents the "angiogenic switch"?

Accepted Answer

Transition from vascular quiescence to active angiogenesis — Early tumors remain small and avascular (in situ) for years. The angiogenic switch terminates this quiescence, involving increased pro-angiogenic factors and/or loss of inhibitors.

Question 39

In epithelial-to-mesenchymal transition (EMT), cancer cells

Accepted Answer

Gain migratory and invasive properties — EMT involves loss of epithelial characteristics (including E-cadherin) and acquisition of mesenchymal features, enhancing cell motility, invasion, and metastatic potential.

Question 40

The main difference between extrinsic and intrinsic apoptosis pathways is

Accepted Answer

Extrinsic is initiated by death receptors; intrinsic by mitochondrial signals — Extrinsic apoptosis is triggered by death receptors (e.g., Fas), while intrinsic apoptosis is initiated by mitochondrial outer membrane permeabilization. Both activate caspase cascades.

Question 41

Cyclin E primarily functions in the cell cycle to

Accepted Answer

Stimulate DNA synthesis at G1/S transition — Cyclin E, activated by E2F, forms cyclin E-CDK2 complex that promotes progression through S phase and DNA synthesis. It acts after cyclin D initiates RB phosphorylation.

Question 42

Amplification of the CDK4 gene has been observed in

Accepted Answer

Sarcomas and glioblastomas specifically — CDK4 gene amplification is particularly noted in sarcomas and glioblastomas, contributing to uncontrolled cell cycle progression through excessive RB phosphorylation.

Question 43

Patients with Bloom syndrome, ataxia-telangiectasia, and Fanconi anemia share which common characteristic?

Accepted Answer

Defects in homologous recombination repair and hypersensitivity to DNA damage — These syndromes involve defects in homologous recombination DNA repair, causing genomic instability, hypersensitivity to DNA-damaging agents, and increased cancer risk.

Question 44

Why do tumor cells in the bloodstream often form emboli with leukocytes and platelets?

Accepted Answer

To gain protection from immune effector cells — Aggregation with leukocytes and platelets provides tumor cells some protection from antitumor immune effector cells during circulation, improving survival and metastatic potential.

Question 45

The invasion-metastasis cascade can be interrupted at multiple points. Which is NOT a step in this cascade?

Accepted Answer

Increased cell-cell adhesion — The metastatic cascade involves loosening of cell-cell contacts (not increased adhesion), local invasion, intravasation, transit, extravasation, and growth at distant sites.

Question 46

COX-2 inhibitors are being investigated for cancer prevention because

Accepted Answer

COX-2 expression is induced by inflammation and increased in many tumors — COX-2 converts arachidonic acid to prostaglandins and is induced by inflammatory stimuli. It's overexpressed in colon and other cancers, linking inflammation to carcinogenesis.

Question 47

Which mechanism does NOT contribute to loosening of tumor cell-to-cell contacts during invasion?

Accepted Answer

Overexpression of integrins for basement membrane — Loss of E-cadherin function (through mutation, β-catenin activation, or SNAIL/TWIST expression) loosens cell-cell contacts. Integrin expression relates to cell-ECM interactions, not cell-cell adhesion.

Question 48

Chemokine receptor CXCR4 is highly expressed on breast cancer cells. This receptor's ligand CXCL12 is expressed in organs where breast cancer commonly metastasizes. This exemplifies

Accepted Answer

Organ tropism guided by chemokine signaling — This explains organ-specific metastasis: cancer cells expressing certain chemokine receptors are attracted to organs expressing the corresponding chemokines, determining metastatic patterns.

Question 49

The concept that metastatic potential may be an intrinsic property developed early in carcinogenesis challenges which traditional view?

Accepted Answer

That metastasis requires stochastic generation of metastatic subclones late in tumor progression — Gene expression profiling suggests some tumors acquire metastatic signatures early during carcinogenesis, not just through late-stage random mutations generating metastatic subclones.

Question 50

BRCA1 and BRCA2 mutations predispose to breast cancer because these genes are involved in

Accepted Answer

DNA repair by homologous recombination — BRCA1 and BRCA2 are involved in DNA repair by homologous recombination. Mutations lead to genomic instability and accumulation of additional mutations, increasing cancer risk.

ONCOPATHOLOGY MCQ EXAMINATION HAllmarks of Cancer 1,2 &amp;3 | MCQ Quiz | OmpathStudy Kenya

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ONCOPATHOLOGY MCQ EXAMINATION HAllmarks of Cancer 1,2 &3 | MCQ Quiz | OmpathStudy Kenya