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
Chapter 1 — The Genome
Question: A 28-year-old woman undergoes genetic testing after
a family history of hereditary breast cancer. A pathogenic
variant is found that alters a tumor suppressor gene resulting in
loss of function. Which mechanism most likely explains how
loss of a tumor suppressor increases cancer risk?
A. Increased enzyme activity that promotes proliferation
B. Failure to repair DNA damage and unchecked cell-cycle
progression
C. Enhanced ligand-independent receptor activation
D. Upregulation of mitochondrial oxidative phosphorylation
Correct Answer: B
Rationales:
, • B (correct): Tumor suppressor loss impairs DNA damage
checkpoints and repair pathways, permitting propagation
of mutations and uncontrolled cell-cycle progression. This
is the classic “two-hit” concept described for tumor
suppressors. (Robbins Ch.1, The Genome — tumor
suppressors and genome integrity).
• A: Increased enzyme activity promoting proliferation is
typical of activated oncogenes, not loss of tumor
suppressors.
• C: Ligand-independent receptor activation is a common
oncogene mechanism (e.g., receptor tyrosine kinase
mutation), not the primary effect of tumor suppressor
loss.
• D: Upregulated oxidative phosphorylation is not the
primary route by which tumor suppressor loss drives early
carcinogenesis.
Teaching Point: Tumor suppressor loss removes brakes on DNA
repair and cell-cycle control.
Citation: Robbins & Cotran Pathologic Basis of Disease, 10th
Ed., Chapter 1 — The Genome (tumor suppressors and cell-
cycle checkpoints).
2. Chapter 1 — Cellular Housekeeping: Ubiquitin–Proteasome
System
,Question: An elderly patient with weight loss and muscle
wasting is started on bortezomib for multiple myeloma. Which
cellular process does bortezomib primarily inhibit that explains
part of its antitumor effect?
A. Lysosomal degradation via autophagy
B. Ubiquitin-mediated proteasomal degradation of regulatory
proteins
C. Endoplasmic reticulum protein folding by chaperones
D. Mitochondrial ATP synthesis
Correct Answer: B
Rationales:
• B (correct): Bortezomib inhibits the 26S proteasome,
preventing ubiquitin-tagged protein degradation, leading
to accumulation of misfolded/regulatory proteins and
apoptosis of malignant plasma cells. (Robbins Ch.1,
Cellular housekeeping — proteasome).
• A: Autophagy is lysosome-mediated and a different
degradation pathway; bortezomib targets the proteasome.
• C: Chaperone-mediated folding occurs in ER; proteasome
inhibition affects downstream protein turnover rather
than chaperone activity.
• D: Proteasome inhibitors do not directly block
mitochondrial ATP production.
Teaching Point: Proteasome inhibition blocks ubiquitin-tagged
protein degradation, promoting tumor cell death.
, Citation: Robbins Ch.1 — Cellular Housekeeping (ubiquitin–
proteasome system).
3. Chapter 1 — Cellular Housekeeping: Autophagy
Question: A patient with prolonged nutritional deprivation
shows increased autophagic vacuoles in hepatocytes on biopsy.
What is the main adaptive role of autophagy in this setting?
A. Trigger immediate necrosis to release nutrients
B. Sequester and degrade cytoplasmic components to recycle
substrates
C. Activate the ubiquitin–proteasome system to synthesize
proteins
D. Increase mitochondrial biogenesis to boost ATP
Correct Answer: B
Rationales:
• B (correct): During starvation, autophagy sequesters
cytoplasmic organelles and proteins into autophagosomes
that fuse with lysosomes for degradation, recycling amino
acids and other substrates for energy and survival.
(Robbins Ch.1, Cellular housekeeping — autophagy).
• A: Autophagy is a survival mechanism, not a trigger for
necrosis.
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter 1 — The Genome
Question: A 28-year-old woman undergoes genetic testing after
a family history of hereditary breast cancer. A pathogenic
variant is found that alters a tumor suppressor gene resulting in
loss of function. Which mechanism most likely explains how
loss of a tumor suppressor increases cancer risk?
A. Increased enzyme activity that promotes proliferation
B. Failure to repair DNA damage and unchecked cell-cycle
progression
C. Enhanced ligand-independent receptor activation
D. Upregulation of mitochondrial oxidative phosphorylation
Correct Answer: B
Rationales:
, • B (correct): Tumor suppressor loss impairs DNA damage
checkpoints and repair pathways, permitting propagation
of mutations and uncontrolled cell-cycle progression. This
is the classic “two-hit” concept described for tumor
suppressors. (Robbins Ch.1, The Genome — tumor
suppressors and genome integrity).
• A: Increased enzyme activity promoting proliferation is
typical of activated oncogenes, not loss of tumor
suppressors.
• C: Ligand-independent receptor activation is a common
oncogene mechanism (e.g., receptor tyrosine kinase
mutation), not the primary effect of tumor suppressor
loss.
• D: Upregulated oxidative phosphorylation is not the
primary route by which tumor suppressor loss drives early
carcinogenesis.
Teaching Point: Tumor suppressor loss removes brakes on DNA
repair and cell-cycle control.
Citation: Robbins & Cotran Pathologic Basis of Disease, 10th
Ed., Chapter 1 — The Genome (tumor suppressors and cell-
cycle checkpoints).
2. Chapter 1 — Cellular Housekeeping: Ubiquitin–Proteasome
System
,Question: An elderly patient with weight loss and muscle
wasting is started on bortezomib for multiple myeloma. Which
cellular process does bortezomib primarily inhibit that explains
part of its antitumor effect?
A. Lysosomal degradation via autophagy
B. Ubiquitin-mediated proteasomal degradation of regulatory
proteins
C. Endoplasmic reticulum protein folding by chaperones
D. Mitochondrial ATP synthesis
Correct Answer: B
Rationales:
• B (correct): Bortezomib inhibits the 26S proteasome,
preventing ubiquitin-tagged protein degradation, leading
to accumulation of misfolded/regulatory proteins and
apoptosis of malignant plasma cells. (Robbins Ch.1,
Cellular housekeeping — proteasome).
• A: Autophagy is lysosome-mediated and a different
degradation pathway; bortezomib targets the proteasome.
• C: Chaperone-mediated folding occurs in ER; proteasome
inhibition affects downstream protein turnover rather
than chaperone activity.
• D: Proteasome inhibitors do not directly block
mitochondrial ATP production.
Teaching Point: Proteasome inhibition blocks ubiquitin-tagged
protein degradation, promoting tumor cell death.
, Citation: Robbins Ch.1 — Cellular Housekeeping (ubiquitin–
proteasome system).
3. Chapter 1 — Cellular Housekeeping: Autophagy
Question: A patient with prolonged nutritional deprivation
shows increased autophagic vacuoles in hepatocytes on biopsy.
What is the main adaptive role of autophagy in this setting?
A. Trigger immediate necrosis to release nutrients
B. Sequester and degrade cytoplasmic components to recycle
substrates
C. Activate the ubiquitin–proteasome system to synthesize
proteins
D. Increase mitochondrial biogenesis to boost ATP
Correct Answer: B
Rationales:
• B (correct): During starvation, autophagy sequesters
cytoplasmic organelles and proteins into autophagosomes
that fuse with lysosomes for degradation, recycling amino
acids and other substrates for energy and survival.
(Robbins Ch.1, Cellular housekeeping — autophagy).
• A: Autophagy is a survival mechanism, not a trigger for
necrosis.
