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
1. Question: A 45-year-old man presents with progressive
muscle weakness. Genetic testing shows a trinucleotide
repeat expansion in an expressed gene. Which mechanism
best explains how an expanded coding repeat causes
disease?
A. Loss of gene promoter activity leading to no mRNA
production
B. Production of an abnormally long, misfolded protein
with toxic properties
C. Increased DNA methylation that permanently silences
the gene
D. Enhanced homologous recombination causing
chromosomal deletions
Correct Answer: B — Production of an abnormally long,
misfolded protein with toxic properties
,Rationales:
• Correct: Expanded coding trinucleotide repeats (e.g., CAG)
produce elongated proteins prone to misfolding and toxic
gain-of-function effects, causing cellular dysfunction.
(Robbins Ch.1, The Genome).
• A: Loss of promoter activity is not the main effect of
coding repeat expansions; those affect protein sequence
rather than transcription initiation.
• C: Repeat expansions in promoters can cause methylation
(a mechanism in some disorders), but coding expansions
primarily alter the protein product.
• D: Expanded repeats do not typically cause enhanced
homologous recombination leading to deletions as the
primary pathogenic mechanism.
Teaching Point: Coding trinucleotide expansions often cause
toxic gain-of-function misfolded proteins.
Citation: Robbins & Cotran, 10th ed., Ch.1 — The Genome
2. Chapter 1 — The Genome
Question: A tumor sample demonstrates high levels of
double-strand DNA breaks and chromosomal
translocations. Which DNA repair defect most likely
contributes to this pattern?
A. Defective base excision repair
B. Defective nucleotide excision repair
C. Defective nonhomologous end joining (NHEJ)
D. Defective mismatch repair
,Correct Answer: C — Defective nonhomologous end joining
(NHEJ)
Rationales:
• Correct: NHEJ repairs double-strand breaks; defects lead to
persistent breaks and chromosomal
rearrangements/translocations. (Robbins Ch.1, The
Genome).
• A: Base excision repair corrects small base lesions, not
double-strand breaks.
• B: Nucleotide excision repair removes bulky helix-
distorting lesions but does not primarily repair double-
strand breaks.
• D: Mismatch repair corrects replication errors and causes
microsatellite instability rather than chromosomal
translocations.
Teaching Point: NHEJ defects predispose to chromosomal
instability and translocations.
Citation: Robbins & Cotran, 10th ed., Ch.1 — The Genome
3. Chapter 1 — Cellular Housekeeping
Question: A patient’s liver biopsy shows accumulation of
ubiquitin-positive protein aggregates in hepatocytes. Which
intracellular pathway is most directly impaired?
A. Autophagy-lysosomal pathway
B. Endoplasmic reticulum (ER) calcium release
C. Proteasomal (ubiquitin-proteasome) degradation
D. Clathrin-mediated endocytosis
, Correct Answer: C — Proteasomal (ubiquitin-proteasome)
degradation
Rationales:
• Correct: Ubiquitin tags direct misfolded proteins to the
proteasome; accumulation of ubiquitin-positive aggregates
indicates proteasomal dysfunction. (Robbins Ch.1, Cellular
Housekeeping).
• A: Autophagy handles larger structures and organelles;
ubiquitin-positive small aggregates classically implicate the
proteasome.
• B: ER calcium dysregulation can cause stress but does not
directly explain ubiquitin-tagged aggregate accumulation.
• D: Clathrin-mediated endocytosis is for membrane
internalization, unrelated to cytosolic ubiquitin-tagged
protein degradation.
Teaching Point: Ubiquitin accumulation signals impaired
proteasomal degradation of misfolded proteins.
Citation: Robbins & Cotran, 10th ed., Ch.1 — Cellular
Housekeeping
4. Chapter 1 — Cellular Metabolism and Mitochondrial
Function
Question: A patient with progressive lactic acidosis and
neurodegeneration is found to have decreased activity of
mitochondrial complex I. Which cellular consequence best
explains the lactic acidosis?
A. Increased β-oxidation of fatty acids producing ketones
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
1. Question: A 45-year-old man presents with progressive
muscle weakness. Genetic testing shows a trinucleotide
repeat expansion in an expressed gene. Which mechanism
best explains how an expanded coding repeat causes
disease?
A. Loss of gene promoter activity leading to no mRNA
production
B. Production of an abnormally long, misfolded protein
with toxic properties
C. Increased DNA methylation that permanently silences
the gene
D. Enhanced homologous recombination causing
chromosomal deletions
Correct Answer: B — Production of an abnormally long,
misfolded protein with toxic properties
,Rationales:
• Correct: Expanded coding trinucleotide repeats (e.g., CAG)
produce elongated proteins prone to misfolding and toxic
gain-of-function effects, causing cellular dysfunction.
(Robbins Ch.1, The Genome).
• A: Loss of promoter activity is not the main effect of
coding repeat expansions; those affect protein sequence
rather than transcription initiation.
• C: Repeat expansions in promoters can cause methylation
(a mechanism in some disorders), but coding expansions
primarily alter the protein product.
• D: Expanded repeats do not typically cause enhanced
homologous recombination leading to deletions as the
primary pathogenic mechanism.
Teaching Point: Coding trinucleotide expansions often cause
toxic gain-of-function misfolded proteins.
Citation: Robbins & Cotran, 10th ed., Ch.1 — The Genome
2. Chapter 1 — The Genome
Question: A tumor sample demonstrates high levels of
double-strand DNA breaks and chromosomal
translocations. Which DNA repair defect most likely
contributes to this pattern?
A. Defective base excision repair
B. Defective nucleotide excision repair
C. Defective nonhomologous end joining (NHEJ)
D. Defective mismatch repair
,Correct Answer: C — Defective nonhomologous end joining
(NHEJ)
Rationales:
• Correct: NHEJ repairs double-strand breaks; defects lead to
persistent breaks and chromosomal
rearrangements/translocations. (Robbins Ch.1, The
Genome).
• A: Base excision repair corrects small base lesions, not
double-strand breaks.
• B: Nucleotide excision repair removes bulky helix-
distorting lesions but does not primarily repair double-
strand breaks.
• D: Mismatch repair corrects replication errors and causes
microsatellite instability rather than chromosomal
translocations.
Teaching Point: NHEJ defects predispose to chromosomal
instability and translocations.
Citation: Robbins & Cotran, 10th ed., Ch.1 — The Genome
3. Chapter 1 — Cellular Housekeeping
Question: A patient’s liver biopsy shows accumulation of
ubiquitin-positive protein aggregates in hepatocytes. Which
intracellular pathway is most directly impaired?
A. Autophagy-lysosomal pathway
B. Endoplasmic reticulum (ER) calcium release
C. Proteasomal (ubiquitin-proteasome) degradation
D. Clathrin-mediated endocytosis
, Correct Answer: C — Proteasomal (ubiquitin-proteasome)
degradation
Rationales:
• Correct: Ubiquitin tags direct misfolded proteins to the
proteasome; accumulation of ubiquitin-positive aggregates
indicates proteasomal dysfunction. (Robbins Ch.1, Cellular
Housekeeping).
• A: Autophagy handles larger structures and organelles;
ubiquitin-positive small aggregates classically implicate the
proteasome.
• B: ER calcium dysregulation can cause stress but does not
directly explain ubiquitin-tagged aggregate accumulation.
• D: Clathrin-mediated endocytosis is for membrane
internalization, unrelated to cytosolic ubiquitin-tagged
protein degradation.
Teaching Point: Ubiquitin accumulation signals impaired
proteasomal degradation of misfolded proteins.
Citation: Robbins & Cotran, 10th ed., Ch.1 — Cellular
Housekeeping
4. Chapter 1 — Cellular Metabolism and Mitochondrial
Function
Question: A patient with progressive lactic acidosis and
neurodegeneration is found to have decreased activity of
mitochondrial complex I. Which cellular consequence best
explains the lactic acidosis?
A. Increased β-oxidation of fatty acids producing ketones
