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. Stem: A 35-year-old patient has familial colon cancer with
germline loss-of-function in a DNA mismatch-repair gene
(MSH2). Which genomic consequence most directly
explains the tumor’s high mutational burden?
A. Increased chromosomal aneuploidy
B. Accumulation of single-nucleotide substitutions at
microsatellite repeats
C. Activation of oncogenic retrotransposons
D. Loss of heterochromatin leading to global gene
activation
Correct Answer: B
Rationale (correct): Defective mismatch repair leads to failure
to correct replication errors, causing microsatellite instability
,and accumulation of single-nucleotide insertions/deletions and
substitutions at repetitive sequences, increasing mutational
burden. This mechanism is described in Robbins’ discussion of
DNA repair and genome integrity. morfopatologie.usmf.md
Rationale (A): Aneuploidy arises from mitotic segregation
errors and is not the primary result of mismatch-repair defects.
Rationale (C): Retrotransposon activation is a different
mutational mechanism and not the hallmark of MMR
deficiency.
Rationale (D): Heterochromatin loss alters gene expression
broadly but does not specifically produce the microsatellite
mutations seen with MSH2 loss.
Teaching Point: Mismatch-repair loss → microsatellite
instability and high rates of replication errors.
Citation: Robbins & Cotran, Ch.1 “The Genome.”
morfopatologie.usmf.md
2. Chapter 1 — The Genome
Stem: A researcher finds a single-base change in a
noncoding regulatory region that reduces transcription
factor binding and lowers protein expression. This variant
is best classified as which type of genomic change?
A. Nonsense mutation
B. Synonymous coding SNP
C. Regulatory noncoding variant
D. Frameshift deletion
,Correct Answer: C
Rationale (correct): Variants in noncoding regulatory elements
(promoters/enhancers) can alter transcription factor binding
and gene expression without changing coding sequence;
Robbins emphasizes the functional importance of noncoding
DNA. morfopatologie.usmf.md
Rationale (A): A nonsense mutation creates a stop codon
within coding sequence, not a regulatory effect.
Rationale (B): A synonymous SNP is within coding sequence
and typically does not change TF binding at regulatory regions.
Rationale (D): Frameshifts alter the reading frame in coding
regions; they don’t describe noncoding regulatory changes.
Teaching Point: Noncoding variants can critically alter gene
expression by disrupting regulatory elements.
Citation: Robbins & Cotran, Ch.1 “The Genome.”
morfopatologie.usmf.md
3. Chapter 1 — Cellular Housekeeping
Stem: A neuron accumulates ubiquitinated, misfolded
proteins due to proteasome inhibition. Which cellular
consequence explains neurotoxicity in this scenario?
A. Increased autophagic flux clearing aggregates
B. Proteotoxic stress triggering unfolded protein response
and cell death pathways
C. Elevated lysosomal degradation compensating for
, proteasome loss
D. Enhanced mitochondrial biogenesis neutralizing
aggregates
Correct Answer: B
Rationale (correct): Proteasome inhibition causes accumulation
of misfolded, ubiquitinated proteins, provoking ER
stress/unfolded protein response and proteotoxicity that can
lead to apoptosis — a mechanism detailed under cellular
housekeeping and protein quality control.
morfopatologie.usmf.md
Rationale (A): Autophagy may be induced but is often
insufficient to clear all aggregates; proteasome blockade
primarily causes proteotoxic stress.
Rationale (C): Lysosomal degradation can help but does not
fully compensate for proteasome failure in neurons.
Rationale (D): Mitochondrial biogenesis doesn’t directly
eliminate cytosolic protein aggregates.
Teaching Point: Proteasome failure → unfolded protein
response and proteotoxic cell injury.
Citation: Robbins & Cotran, Ch.1 “Cellular Housekeeping.”
morfopatologie.usmf.md
4. Chapter 1 — Cellular Housekeeping (Lysosomes)
Stem: A patient has a lysosomal storage disorder with
deficient acid hydrolase activity. Which intracellular
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. Stem: A 35-year-old patient has familial colon cancer with
germline loss-of-function in a DNA mismatch-repair gene
(MSH2). Which genomic consequence most directly
explains the tumor’s high mutational burden?
A. Increased chromosomal aneuploidy
B. Accumulation of single-nucleotide substitutions at
microsatellite repeats
C. Activation of oncogenic retrotransposons
D. Loss of heterochromatin leading to global gene
activation
Correct Answer: B
Rationale (correct): Defective mismatch repair leads to failure
to correct replication errors, causing microsatellite instability
,and accumulation of single-nucleotide insertions/deletions and
substitutions at repetitive sequences, increasing mutational
burden. This mechanism is described in Robbins’ discussion of
DNA repair and genome integrity. morfopatologie.usmf.md
Rationale (A): Aneuploidy arises from mitotic segregation
errors and is not the primary result of mismatch-repair defects.
Rationale (C): Retrotransposon activation is a different
mutational mechanism and not the hallmark of MMR
deficiency.
Rationale (D): Heterochromatin loss alters gene expression
broadly but does not specifically produce the microsatellite
mutations seen with MSH2 loss.
Teaching Point: Mismatch-repair loss → microsatellite
instability and high rates of replication errors.
Citation: Robbins & Cotran, Ch.1 “The Genome.”
morfopatologie.usmf.md
2. Chapter 1 — The Genome
Stem: A researcher finds a single-base change in a
noncoding regulatory region that reduces transcription
factor binding and lowers protein expression. This variant
is best classified as which type of genomic change?
A. Nonsense mutation
B. Synonymous coding SNP
C. Regulatory noncoding variant
D. Frameshift deletion
,Correct Answer: C
Rationale (correct): Variants in noncoding regulatory elements
(promoters/enhancers) can alter transcription factor binding
and gene expression without changing coding sequence;
Robbins emphasizes the functional importance of noncoding
DNA. morfopatologie.usmf.md
Rationale (A): A nonsense mutation creates a stop codon
within coding sequence, not a regulatory effect.
Rationale (B): A synonymous SNP is within coding sequence
and typically does not change TF binding at regulatory regions.
Rationale (D): Frameshifts alter the reading frame in coding
regions; they don’t describe noncoding regulatory changes.
Teaching Point: Noncoding variants can critically alter gene
expression by disrupting regulatory elements.
Citation: Robbins & Cotran, Ch.1 “The Genome.”
morfopatologie.usmf.md
3. Chapter 1 — Cellular Housekeeping
Stem: A neuron accumulates ubiquitinated, misfolded
proteins due to proteasome inhibition. Which cellular
consequence explains neurotoxicity in this scenario?
A. Increased autophagic flux clearing aggregates
B. Proteotoxic stress triggering unfolded protein response
and cell death pathways
C. Elevated lysosomal degradation compensating for
, proteasome loss
D. Enhanced mitochondrial biogenesis neutralizing
aggregates
Correct Answer: B
Rationale (correct): Proteasome inhibition causes accumulation
of misfolded, ubiquitinated proteins, provoking ER
stress/unfolded protein response and proteotoxicity that can
lead to apoptosis — a mechanism detailed under cellular
housekeeping and protein quality control.
morfopatologie.usmf.md
Rationale (A): Autophagy may be induced but is often
insufficient to clear all aggregates; proteasome blockade
primarily causes proteotoxic stress.
Rationale (C): Lysosomal degradation can help but does not
fully compensate for proteasome failure in neurons.
Rationale (D): Mitochondrial biogenesis doesn’t directly
eliminate cytosolic protein aggregates.
Teaching Point: Proteasome failure → unfolded protein
response and proteotoxic cell injury.
Citation: Robbins & Cotran, Ch.1 “Cellular Housekeeping.”
morfopatologie.usmf.md
4. Chapter 1 — Cellular Housekeeping (Lysosomes)
Stem: A patient has a lysosomal storage disorder with
deficient acid hydrolase activity. Which intracellular
