Robbins Basic Pathology
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1)
Reference — Ch. 1 — The Genome
Question Stem — A 28-year-old pregnant patient undergoes
noninvasive prenatal testing that detects a high level of
fragmented fetal DNA carrying a frameshift mutation in a gene
required for hemoglobin synthesis. Which genomic mechanism
best explains how a frameshift mutation could produce a
dysfunctional protein?
Options
A. Gain-of-function mutation altering regulatory promoter
activity
,B. Single-base substitution producing a premature stop codon
(nonsense)
C. Insertion or deletion of nucleotides shifting the reading
frame downstream
D. Expansion of trinucleotide repeats in a noncoding intron
Correct Answer — C
Rationales — Correct: Frameshift mutations result from
insertions or deletions (not divisible by three) and change the
downstream codon reading frame, usually producing abnormal
amino acid sequence and truncated or nonfunctional proteins.
Incorrect A: Gain-of-function in promoters alters expression
level rather than shifting codon reading frames.
Incorrect B: A single-base substitution causing a stop codon is a
nonsense mutation, not a frameshift.
Incorrect D: Trinucleotide repeat expansion causes disease via
repeat expansion mechanisms, usually in coding or regulatory
regions, not classical frameshift.
Teaching Point — Insertions/deletions (not in multiples of
three) shift coding frames and disable proteins.
Citation — Kumar et al. (2021). Robbins Basic Pathology (10th
Ed.). Ch. 1.
2)
Reference — Ch. 1 — The Genome
Question Stem — A patient’s tumor sample shows loss of
heterozygosity at a tumor suppressor locus. Clinically, which
,consequence most likely follows this genomic alteration?
Options
A. Increased expression of a proto-oncogene leading to
proliferation
B. Complete loss of function of a growth-inhibitory protein
enabling clonal expansion
C. Increased DNA repair capacity reducing mutation burden
D. Expression of a dominant-negative protein that blocks
apoptosis only in heterozygotes
Correct Answer — B
Rationales — Correct: Loss of heterozygosity eliminates the
remaining functional allele of a tumor suppressor, removing
growth inhibition and permitting unchecked proliferation.
Incorrect A: Proto-oncogene activation is usually from gain-of-
function events, not LOH of tumor suppressors.
Incorrect C: LOH reduces tumor suppressor activity and typically
impairs genomic stability rather than enhancing repair.
Incorrect D: Dominant-negative effects are specific mutation
types; LOH describes loss, not creation, of dominant-negative
proteins.
Teaching Point — LOH removes tumor suppressor function,
promoting neoplastic growth.
Citation — Kumar et al. (2021). Robbins Basic Pathology (10th
Ed.). Ch. 1.
, 3)
Reference — Ch. 1 — Cellular Housekeeping
Question Stem — A 65-year-old man with chronic alcohol use
presents with hepatocellular injury and prominent Mallory
bodies in hepatocytes. Which cellular housekeeping failure
most directly contributes to accumulation of misfolded
cytoskeletal proteins?
Options
A. Increased lysosomal acid hydrolase activity
B. Impaired ubiquitin–proteasome degradation of cytoskeletal
proteins
C. Enhanced autophagy of aggregated proteins
D. Upregulated chaperone-mediated folding preventing
aggregation
Correct Answer — B
Rationales — Correct: Impaired ubiquitin-proteasome pathway
reduces degradation of damaged or misfolded cytoskeletal
proteins, promoting their aggregation (e.g., Mallory bodies).
Incorrect A: Increased lysosomal activity would tend to clear,
not accumulate, proteins.
Incorrect C: Enhanced autophagy would decrease aggregates;
Mallory bodies reflect insufficient clearance.
Incorrect D: Upregulated chaperones improve folding and
reduce aggregation, opposite of the pathology.
Teaching Point — Ubiquitin–proteasome failure causes
cytoskeletal protein aggregation.
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1)
Reference — Ch. 1 — The Genome
Question Stem — A 28-year-old pregnant patient undergoes
noninvasive prenatal testing that detects a high level of
fragmented fetal DNA carrying a frameshift mutation in a gene
required for hemoglobin synthesis. Which genomic mechanism
best explains how a frameshift mutation could produce a
dysfunctional protein?
Options
A. Gain-of-function mutation altering regulatory promoter
activity
,B. Single-base substitution producing a premature stop codon
(nonsense)
C. Insertion or deletion of nucleotides shifting the reading
frame downstream
D. Expansion of trinucleotide repeats in a noncoding intron
Correct Answer — C
Rationales — Correct: Frameshift mutations result from
insertions or deletions (not divisible by three) and change the
downstream codon reading frame, usually producing abnormal
amino acid sequence and truncated or nonfunctional proteins.
Incorrect A: Gain-of-function in promoters alters expression
level rather than shifting codon reading frames.
Incorrect B: A single-base substitution causing a stop codon is a
nonsense mutation, not a frameshift.
Incorrect D: Trinucleotide repeat expansion causes disease via
repeat expansion mechanisms, usually in coding or regulatory
regions, not classical frameshift.
Teaching Point — Insertions/deletions (not in multiples of
three) shift coding frames and disable proteins.
Citation — Kumar et al. (2021). Robbins Basic Pathology (10th
Ed.). Ch. 1.
2)
Reference — Ch. 1 — The Genome
Question Stem — A patient’s tumor sample shows loss of
heterozygosity at a tumor suppressor locus. Clinically, which
,consequence most likely follows this genomic alteration?
Options
A. Increased expression of a proto-oncogene leading to
proliferation
B. Complete loss of function of a growth-inhibitory protein
enabling clonal expansion
C. Increased DNA repair capacity reducing mutation burden
D. Expression of a dominant-negative protein that blocks
apoptosis only in heterozygotes
Correct Answer — B
Rationales — Correct: Loss of heterozygosity eliminates the
remaining functional allele of a tumor suppressor, removing
growth inhibition and permitting unchecked proliferation.
Incorrect A: Proto-oncogene activation is usually from gain-of-
function events, not LOH of tumor suppressors.
Incorrect C: LOH reduces tumor suppressor activity and typically
impairs genomic stability rather than enhancing repair.
Incorrect D: Dominant-negative effects are specific mutation
types; LOH describes loss, not creation, of dominant-negative
proteins.
Teaching Point — LOH removes tumor suppressor function,
promoting neoplastic growth.
Citation — Kumar et al. (2021). Robbins Basic Pathology (10th
Ed.). Ch. 1.
, 3)
Reference — Ch. 1 — Cellular Housekeeping
Question Stem — A 65-year-old man with chronic alcohol use
presents with hepatocellular injury and prominent Mallory
bodies in hepatocytes. Which cellular housekeeping failure
most directly contributes to accumulation of misfolded
cytoskeletal proteins?
Options
A. Increased lysosomal acid hydrolase activity
B. Impaired ubiquitin–proteasome degradation of cytoskeletal
proteins
C. Enhanced autophagy of aggregated proteins
D. Upregulated chaperone-mediated folding preventing
aggregation
Correct Answer — B
Rationales — Correct: Impaired ubiquitin-proteasome pathway
reduces degradation of damaged or misfolded cytoskeletal
proteins, promoting their aggregation (e.g., Mallory bodies).
Incorrect A: Increased lysosomal activity would tend to clear,
not accumulate, proteins.
Incorrect C: Enhanced autophagy would decrease aggregates;
Mallory bodies reflect insufficient clearance.
Incorrect D: Upregulated chaperones improve folding and
reduce aggregation, opposite of the pathology.
Teaching Point — Ubiquitin–proteasome failure causes
cytoskeletal protein aggregation.
