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
Stem: A 32-year-old woman receives diagnostic radiation
exposure. Which mechanism best explains how ionizing
radiation increases the risk of permanent mutations in somatic
cells?
A. Formation of thymine dimers that block replication
B. Single- and double-strand DNA breaks causing misrepair
C. Direct alkylation of guanine leading to base mispairing
D. Increased CpG methylation silencing tumor suppressors
Correct Answer: B
Rationale (correct): Ionizing radiation produces free radicals
that induce single- and double-strand DNA breaks; erroneous
repair of double-strand breaks leads to deletions,
translocations, and permanent mutations. This mechanism is
,the primary way radiation causes mutagenesis and genomic
instability. (Robbins — Chapter 1: The Genome)
Incorrect options:
A — Thymine dimers are caused primarily by ultraviolet
radiation, not ionizing radiation.
C — Alkylation of guanine is typically associated with certain
chemical mutagens, not direct ionizing radiation effects.
D — CpG methylation changes are epigenetic modifications and
not the immediate result of radiation-induced DNA strand
breaks.
Teaching Point: Ionizing radiation causes mutations mainly via
misrepaired DNA strand breaks.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
2. Chapter 1 — The Genome
Stem: A tumor shows microsatellite instability (MSI). Which
cellular defect most likely produced MSI?
A. Defective mismatch repair enzymes
B. Loss of nucleotide excision repair capacity
C. Defective base excision repair glycosylases
D. Impaired non-homologous end-joining
Correct Answer: A
Rationale (correct): Microsatellite instability arises from
defects in mismatch repair proteins (e.g., MSH2, MLH1) that
normally correct replication slippage in repetitive sequences;
,loss produces variable-length microsatellites and increased
mutation rates. This defect is characteristic of certain
hereditary and sporadic cancers. (Robbins — Chapter 1: The
Genome)
Incorrect options:
B — Nucleotide excision repair corrects bulky helix-distorting
lesions (e.g., UV-induced dimers), not replication slippage at
microsatellites.
C — Base excision repair fixes small base lesions (oxidation,
alkylation), not MSI.
D — Non-homologous end-joining repairs double-strand breaks
and is not the primary cause of MSI.
Teaching Point: Microsatellite instability reflects mismatch
repair failure.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
3. Chapter 1 — Cellular Housekeeping
Stem: A patient with a neurodegenerative disease has
accumulation of ubiquitinated protein aggregates in neurons.
Which impaired cellular process most directly explains this
finding?
A. Lysosomal acid hydrolase deficiency
B. Defect in ubiquitin–proteasome pathway
C. Impaired autophagosome formation only in glia
D. Mitochondrial respiratory chain failure
, Correct Answer: B
Rationale (correct): The ubiquitin–proteasome system tags
misfolded proteins for proteasomal degradation; failure of this
pathway leads to accumulation of ubiquitinated protein
aggregates, a hallmark in several neurodegenerative diseases.
(Robbins — Chapter 1: Cellular Housekeeping)
Incorrect options:
A — Lysosomal hydrolase deficiency (lysosomal storage
diseases) leads to accumulation of undegraded substrates but
not specifically ubiquitinated cytosolic protein aggregates.
C — Autophagy impairment can contribute to aggregate
accumulation, but ubiquitinated aggregates implicate the
proteasome more directly.
D — Mitochondrial failure causes energy deficits and apoptosis
but does not directly produce ubiquitinated protein inclusions.
Teaching Point: The ubiquitin–proteasome pathway clears
misfolded cytosolic proteins.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — Cellular
Housekeeping
4. Chapter 1 — Cellular Housekeeping
Stem: A liver biopsy shows hepatocytes distended with
autophagic vacuoles after fasting and prolonged injury. What
role does autophagy play in stressed cells?
A. It selectively degrades extracellular matrix proteins
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
Stem: A 32-year-old woman receives diagnostic radiation
exposure. Which mechanism best explains how ionizing
radiation increases the risk of permanent mutations in somatic
cells?
A. Formation of thymine dimers that block replication
B. Single- and double-strand DNA breaks causing misrepair
C. Direct alkylation of guanine leading to base mispairing
D. Increased CpG methylation silencing tumor suppressors
Correct Answer: B
Rationale (correct): Ionizing radiation produces free radicals
that induce single- and double-strand DNA breaks; erroneous
repair of double-strand breaks leads to deletions,
translocations, and permanent mutations. This mechanism is
,the primary way radiation causes mutagenesis and genomic
instability. (Robbins — Chapter 1: The Genome)
Incorrect options:
A — Thymine dimers are caused primarily by ultraviolet
radiation, not ionizing radiation.
C — Alkylation of guanine is typically associated with certain
chemical mutagens, not direct ionizing radiation effects.
D — CpG methylation changes are epigenetic modifications and
not the immediate result of radiation-induced DNA strand
breaks.
Teaching Point: Ionizing radiation causes mutations mainly via
misrepaired DNA strand breaks.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
2. Chapter 1 — The Genome
Stem: A tumor shows microsatellite instability (MSI). Which
cellular defect most likely produced MSI?
A. Defective mismatch repair enzymes
B. Loss of nucleotide excision repair capacity
C. Defective base excision repair glycosylases
D. Impaired non-homologous end-joining
Correct Answer: A
Rationale (correct): Microsatellite instability arises from
defects in mismatch repair proteins (e.g., MSH2, MLH1) that
normally correct replication slippage in repetitive sequences;
,loss produces variable-length microsatellites and increased
mutation rates. This defect is characteristic of certain
hereditary and sporadic cancers. (Robbins — Chapter 1: The
Genome)
Incorrect options:
B — Nucleotide excision repair corrects bulky helix-distorting
lesions (e.g., UV-induced dimers), not replication slippage at
microsatellites.
C — Base excision repair fixes small base lesions (oxidation,
alkylation), not MSI.
D — Non-homologous end-joining repairs double-strand breaks
and is not the primary cause of MSI.
Teaching Point: Microsatellite instability reflects mismatch
repair failure.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
3. Chapter 1 — Cellular Housekeeping
Stem: A patient with a neurodegenerative disease has
accumulation of ubiquitinated protein aggregates in neurons.
Which impaired cellular process most directly explains this
finding?
A. Lysosomal acid hydrolase deficiency
B. Defect in ubiquitin–proteasome pathway
C. Impaired autophagosome formation only in glia
D. Mitochondrial respiratory chain failure
, Correct Answer: B
Rationale (correct): The ubiquitin–proteasome system tags
misfolded proteins for proteasomal degradation; failure of this
pathway leads to accumulation of ubiquitinated protein
aggregates, a hallmark in several neurodegenerative diseases.
(Robbins — Chapter 1: Cellular Housekeeping)
Incorrect options:
A — Lysosomal hydrolase deficiency (lysosomal storage
diseases) leads to accumulation of undegraded substrates but
not specifically ubiquitinated cytosolic protein aggregates.
C — Autophagy impairment can contribute to aggregate
accumulation, but ubiquitinated aggregates implicate the
proteasome more directly.
D — Mitochondrial failure causes energy deficits and apoptosis
but does not directly produce ubiquitinated protein inclusions.
Teaching Point: The ubiquitin–proteasome pathway clears
misfolded cytosolic proteins.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — Cellular
Housekeeping
4. Chapter 1 — Cellular Housekeeping
Stem: A liver biopsy shows hepatocytes distended with
autophagic vacuoles after fasting and prolonged injury. What
role does autophagy play in stressed cells?
A. It selectively degrades extracellular matrix proteins
