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 reference: Chapter 1 — The Genome
Stem: A 28-year-old woman has recurrent severe sunburns and
is found to have multiple deletions in nucleotide excision repair
genes. Which cellular consequence best explains her increased
skin cancer risk?
A. Increased rate of homologous recombination during S phase
B. Accumulation of unrepaired UV-induced pyrimidine dimers
leading to mutation fixation
C. Enhanced base excision repair causing point mutations
D. Overactive mismatch repair causing microsatellite instability
Answer: B
Rationale — correct (B): UV light induces pyrimidine (thymine)
dimers that are normally removed by nucleotide excision repair;
,failure permits replication across lesions and fixation of
mutations, increasing cancer risk.
Rationale — incorrect:
A. Homologous recombination repairs double-strand breaks
accurately and its increase would not explain UV-dimer
accumulation.
C. Base excision repair corrects small base lesions (e.g.,
oxidative damage), not bulky UV dimers.
D. Mismatch repair corrects replication errors; overactivity
causing microsatellite instability is not linked to UV-induced
dimers.
Teaching point: Nucleotide excision repair removes bulky DNA
adducts; its failure predisposes to UV-induced mutations.
2)
Chapter reference: Chapter 1 — The Genome
Stem: A tumor shows loss of heterozygosity (LOH) at a
chromosome region containing a tumor suppressor gene.
Which mechanism most likely produced LOH?
A. Gain-of-function mutation in proto-oncogene
B. Chromosomal deletion of the wild-type allele after a
germline mutation in the other allele
C. Promoter methylation activating the tumor suppressor gene
D. Increased expression of a DNA repair enzyme
Answer: B
,Rationale — correct (B): LOH often occurs when the remaining
functional allele is lost (e.g., deletion) after a germline
mutation, eliminating tumor suppressor function (Knudson’s
two-hit).
Rationale — incorrect:
A. Gain-of-function in proto-oncogenes is oncogenic but does
not explain LOH of a tumor suppressor locus.
C. Promoter methylation typically silences genes; methylation
activating a tumor suppressor is incorrect.
D. Increased DNA repair would reduce mutation accumulation,
not cause LOH.
Teaching point: LOH commonly results from deletion of the
remaining wild-type tumor suppressor allele.
3)
Chapter reference: Chapter 1 — Cellular Housekeeping
Stem: A patient with a neurodegenerative disorder has
neuronal accumulation of ubiquitin-positive intracytoplasmic
inclusions. Which defective pathway best explains these
inclusions?
A. Autophagy-lysosomal degradation of organelles
B. Ubiquitin-proteasome pathway for short-lived cytosolic
proteins
C. Endoplasmic reticulum–associated degradation (ERAD) with
intact proteasome
D. Lysosomal uptake of extracellular proteins by pinocytosis
, Answer: B
Rationale — correct (B): Ubiquitin-positive inclusions indicate
proteins tagged for proteasomal degradation that are not
cleared; proteasome dysfunction leads to accumulation
associated with neurodegeneration.
Rationale — incorrect:
A. Autophagy handles large aggregates and organelles;
ubiquitin-positive small protein inclusions more specifically
implicate the proteasome.
C. ERAD channels misfolded ER proteins to the proteasome — if
proteasome is intact this wouldn’t cause inclusions.
D. Pinocytosis is nonspecific uptake of extracellular fluid and not
the main cause of ubiquitin-positive inclusions.
Teaching point: Ubiquitin-proteasome dysfunction causes
intracellular protein aggregate accumulation.
4)
Chapter reference: Chapter 1 — Cellular Housekeeping
Stem: A hepatocyte exposed to a toxin accumulates autophagic
vesicles containing damaged mitochondria. Which statement
best describes autophagy’s immediate role?
A. Direct ubiquitination of mitochondrial proteins for
proteasomal degradation
B. Delivery of damaged organelles to lysosomes for degradation
and nutrient recycling
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter reference: Chapter 1 — The Genome
Stem: A 28-year-old woman has recurrent severe sunburns and
is found to have multiple deletions in nucleotide excision repair
genes. Which cellular consequence best explains her increased
skin cancer risk?
A. Increased rate of homologous recombination during S phase
B. Accumulation of unrepaired UV-induced pyrimidine dimers
leading to mutation fixation
C. Enhanced base excision repair causing point mutations
D. Overactive mismatch repair causing microsatellite instability
Answer: B
Rationale — correct (B): UV light induces pyrimidine (thymine)
dimers that are normally removed by nucleotide excision repair;
,failure permits replication across lesions and fixation of
mutations, increasing cancer risk.
Rationale — incorrect:
A. Homologous recombination repairs double-strand breaks
accurately and its increase would not explain UV-dimer
accumulation.
C. Base excision repair corrects small base lesions (e.g.,
oxidative damage), not bulky UV dimers.
D. Mismatch repair corrects replication errors; overactivity
causing microsatellite instability is not linked to UV-induced
dimers.
Teaching point: Nucleotide excision repair removes bulky DNA
adducts; its failure predisposes to UV-induced mutations.
2)
Chapter reference: Chapter 1 — The Genome
Stem: A tumor shows loss of heterozygosity (LOH) at a
chromosome region containing a tumor suppressor gene.
Which mechanism most likely produced LOH?
A. Gain-of-function mutation in proto-oncogene
B. Chromosomal deletion of the wild-type allele after a
germline mutation in the other allele
C. Promoter methylation activating the tumor suppressor gene
D. Increased expression of a DNA repair enzyme
Answer: B
,Rationale — correct (B): LOH often occurs when the remaining
functional allele is lost (e.g., deletion) after a germline
mutation, eliminating tumor suppressor function (Knudson’s
two-hit).
Rationale — incorrect:
A. Gain-of-function in proto-oncogenes is oncogenic but does
not explain LOH of a tumor suppressor locus.
C. Promoter methylation typically silences genes; methylation
activating a tumor suppressor is incorrect.
D. Increased DNA repair would reduce mutation accumulation,
not cause LOH.
Teaching point: LOH commonly results from deletion of the
remaining wild-type tumor suppressor allele.
3)
Chapter reference: Chapter 1 — Cellular Housekeeping
Stem: A patient with a neurodegenerative disorder has
neuronal accumulation of ubiquitin-positive intracytoplasmic
inclusions. Which defective pathway best explains these
inclusions?
A. Autophagy-lysosomal degradation of organelles
B. Ubiquitin-proteasome pathway for short-lived cytosolic
proteins
C. Endoplasmic reticulum–associated degradation (ERAD) with
intact proteasome
D. Lysosomal uptake of extracellular proteins by pinocytosis
, Answer: B
Rationale — correct (B): Ubiquitin-positive inclusions indicate
proteins tagged for proteasomal degradation that are not
cleared; proteasome dysfunction leads to accumulation
associated with neurodegeneration.
Rationale — incorrect:
A. Autophagy handles large aggregates and organelles;
ubiquitin-positive small protein inclusions more specifically
implicate the proteasome.
C. ERAD channels misfolded ER proteins to the proteasome — if
proteasome is intact this wouldn’t cause inclusions.
D. Pinocytosis is nonspecific uptake of extracellular fluid and not
the main cause of ubiquitin-positive inclusions.
Teaching point: Ubiquitin-proteasome dysfunction causes
intracellular protein aggregate accumulation.
4)
Chapter reference: Chapter 1 — Cellular Housekeeping
Stem: A hepatocyte exposed to a toxin accumulates autophagic
vesicles containing damaged mitochondria. Which statement
best describes autophagy’s immediate role?
A. Direct ubiquitination of mitochondrial proteins for
proteasomal degradation
B. Delivery of damaged organelles to lysosomes for degradation
and nutrient recycling
