Robbins & Cotran 10th Ed. Pathology Test Bank | Chapter-
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1. Chapter Reference — The Genome
Stem: A 3-year-old child presents with recurrent infections
and poor growth. Genetic testing shows a nonsense
mutation producing a premature stop codon in a gene
encoding a critical immune receptor. Which cellular
process most directly explains the reduced receptor
protein levels?
A. Increased proteasomal degradation of the truncated
protein
B. Nonsense-mediated mRNA decay of transcripts with
premature stop codons
C. Increased translation initiation at downstream AUG
codons
D. Enhanced splicing that removes the mutated exon
Answer: B
,Rationale — Correct (B): Nonsense mutations that introduce
premature termination codons commonly trigger nonsense-
mediated mRNA decay (NMD), reducing mRNA and thereby
lowering protein synthesis. This mechanism protects cells from
producing truncated proteins that may be deleterious.
Rationale — Incorrect:
A. Proteasomal degradation could degrade truncated protein
but does not explain reduced mRNA levels; NMD acts upstream.
C. Downstream AUG reinitiation is uncommon in eukaryotes
and would not restore full receptor expression.
D. Enhanced splicing that removes the mutated exon is not a
general consequence of nonsense mutations and would require
alternative splicing machinery.
Teaching Point: Nonsense mutations often reduce protein by
triggering nonsense-mediated mRNA decay.
2. Chapter Reference — The Genome
Stem: A tumor sample shows chromosomal translocation
creating an in-frame fusion protein with constitutive
tyrosine kinase activity. Which mechanism best explains
how this fusion drives neoplastic growth?
A. Loss of tumor suppressor activity due to protein
truncation
B. Constitutive activation of downstream signaling
pathways promoting proliferation
C. Increased DNA repair capacity reducing genomic
, instability
D. Enhanced apoptotic signaling eliminating damaged cells
Answer: B
Rationale — Correct (B): Fusion proteins that include a kinase
domain inappropriately activated lead to continuous signaling
through proliferation and survival pathways (e.g., MAPK, PI3K),
driving neoplastic growth.
Rationale — Incorrect:
A. While truncations can inactivate tumor suppressors, an
activating kinase fusion primarily causes gain-of-function
signaling.
C. Tumor kinase fusions do not increase DNA repair capacity;
they typically promote proliferation despite DNA damage.
D. Constitutive kinase activation generally promotes survival,
not apoptosis.
Teaching Point: Oncogenic fusion kinases drive cancer by
constitutive activation of growth signaling pathways.
3. Chapter Reference — Cellular Housekeeping
Stem: A patient with alpha-antitrypsin deficiency
accumulates misfolded protein in hepatocyte ER. Which
cellular response initially attempts to manage the
misfolded protein load?
A. Autophagic degradation via lysosomes
B. Unfolded protein response with increased chaperone
expression
, C. Immediate initiation of mitochondrial apoptosis
D. Upregulation of proteasome inhibitor proteins
Answer: B
Rationale — Correct (B): Accumulation of misfolded proteins in
the ER activates the unfolded protein response (UPR),
increasing chaperone production, attenuating translation, and
enhancing ER-associated degradation.
Rationale — Incorrect:
A. Autophagy can clear aggregates but the initial, specific ER
response is the UPR.
C. Apoptosis may follow prolonged ER stress, but it is not the
initial adaptive response.
D. Upregulating proteasome inhibitors would worsen
proteotoxic stress; cells typically enhance degradation capacity.
Teaching Point: The unfolded protein response increases
chaperones and reduces protein load during ER stress.
4. Chapter Reference — Cellular Housekeeping
Stem: In neurodegenerative disease, accumulation of
ubiquitinated protein aggregates is observed. Which
pathway is most responsible for targeting soluble
misfolded proteins for degradation under normal
conditions?
A. Lysosomal proteolysis via macroautophagy
B. Ubiquitin-proteasome system degrading
polyubiquitinated proteins
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1. Chapter Reference — The Genome
Stem: A 3-year-old child presents with recurrent infections
and poor growth. Genetic testing shows a nonsense
mutation producing a premature stop codon in a gene
encoding a critical immune receptor. Which cellular
process most directly explains the reduced receptor
protein levels?
A. Increased proteasomal degradation of the truncated
protein
B. Nonsense-mediated mRNA decay of transcripts with
premature stop codons
C. Increased translation initiation at downstream AUG
codons
D. Enhanced splicing that removes the mutated exon
Answer: B
,Rationale — Correct (B): Nonsense mutations that introduce
premature termination codons commonly trigger nonsense-
mediated mRNA decay (NMD), reducing mRNA and thereby
lowering protein synthesis. This mechanism protects cells from
producing truncated proteins that may be deleterious.
Rationale — Incorrect:
A. Proteasomal degradation could degrade truncated protein
but does not explain reduced mRNA levels; NMD acts upstream.
C. Downstream AUG reinitiation is uncommon in eukaryotes
and would not restore full receptor expression.
D. Enhanced splicing that removes the mutated exon is not a
general consequence of nonsense mutations and would require
alternative splicing machinery.
Teaching Point: Nonsense mutations often reduce protein by
triggering nonsense-mediated mRNA decay.
2. Chapter Reference — The Genome
Stem: A tumor sample shows chromosomal translocation
creating an in-frame fusion protein with constitutive
tyrosine kinase activity. Which mechanism best explains
how this fusion drives neoplastic growth?
A. Loss of tumor suppressor activity due to protein
truncation
B. Constitutive activation of downstream signaling
pathways promoting proliferation
C. Increased DNA repair capacity reducing genomic
, instability
D. Enhanced apoptotic signaling eliminating damaged cells
Answer: B
Rationale — Correct (B): Fusion proteins that include a kinase
domain inappropriately activated lead to continuous signaling
through proliferation and survival pathways (e.g., MAPK, PI3K),
driving neoplastic growth.
Rationale — Incorrect:
A. While truncations can inactivate tumor suppressors, an
activating kinase fusion primarily causes gain-of-function
signaling.
C. Tumor kinase fusions do not increase DNA repair capacity;
they typically promote proliferation despite DNA damage.
D. Constitutive kinase activation generally promotes survival,
not apoptosis.
Teaching Point: Oncogenic fusion kinases drive cancer by
constitutive activation of growth signaling pathways.
3. Chapter Reference — Cellular Housekeeping
Stem: A patient with alpha-antitrypsin deficiency
accumulates misfolded protein in hepatocyte ER. Which
cellular response initially attempts to manage the
misfolded protein load?
A. Autophagic degradation via lysosomes
B. Unfolded protein response with increased chaperone
expression
, C. Immediate initiation of mitochondrial apoptosis
D. Upregulation of proteasome inhibitor proteins
Answer: B
Rationale — Correct (B): Accumulation of misfolded proteins in
the ER activates the unfolded protein response (UPR),
increasing chaperone production, attenuating translation, and
enhancing ER-associated degradation.
Rationale — Incorrect:
A. Autophagy can clear aggregates but the initial, specific ER
response is the UPR.
C. Apoptosis may follow prolonged ER stress, but it is not the
initial adaptive response.
D. Upregulating proteasome inhibitors would worsen
proteotoxic stress; cells typically enhance degradation capacity.
Teaching Point: The unfolded protein response increases
chaperones and reduces protein load during ER stress.
4. Chapter Reference — Cellular Housekeeping
Stem: In neurodegenerative disease, accumulation of
ubiquitinated protein aggregates is observed. Which
pathway is most responsible for targeting soluble
misfolded proteins for degradation under normal
conditions?
A. Lysosomal proteolysis via macroautophagy
B. Ubiquitin-proteasome system degrading
polyubiquitinated proteins
