Robbins Basic Pathology
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
Reference — Ch. 1 — The Genome
Question Stem
A 58-year-old man with colorectal cancer shows a tumor with
high microsatellite instability (MSI-high). Which mechanism
best explains why MSI-high tumors accumulate frameshift
mutations in repetitive DNA tracts?
A. Defective nucleotide excision repair leading to thymine dimer
persistence
B. Germline TP53 point mutation causing global genomic
instability
,C. Defective DNA mismatch repair allowing replication slippage
errors to persist
D. Increased homologous recombination that creates repetitive-
sequence expansions
Correct Answer
C
Rationales
• Correct (C): DNA mismatch repair corrects
insertion/deletion loops that occur at repetitive
(microsatellite) sequences during replication; loss of
mismatch repair permits slippage errors to persist,
producing microsatellite instability and frameshift
mutations.
• Incorrect (A): Nucleotide excision repair removes bulky
helix-distorting lesions (e.g., thymine dimers), not
replication slippage at microsatellites.
• Incorrect (B): TP53 mutations cause impaired DNA damage
response but do not specifically cause microsatellite
slippage—the hallmark of MSI is defective mismatch repair.
• Incorrect (D): Homologous recombination repairs double-
strand breaks and does not increase small
insertion/deletion errors at microsatellites.
Teaching Point
Mismatch repair deficiency → unrepaired replication slippage
→ microsatellite instability.
,Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference — Ch. 1 — The Genome
Question Stem
A young adult presents with frequent bacterial infections and is
found to have a nonsense mutation early in a gene required for
innate immune signaling. Which consequence at the molecular
level most directly follows a premature stop (nonsense)
mutation?
A. Production of a truncated polypeptide and possible
nonsense-mediated mRNA decay
B. Increased translation efficiency due to alternative start codon
usage
C. Enhanced promoter activity raising transcription of the
mutant allele
D. Expansion of trinucleotide repeats in the affected gene
Correct Answer
A
Rationales
• Correct (A): Nonsense mutations introduce premature
stop codons that produce truncated proteins; often mRNAs
, with premature stops are targeted by nonsense-mediated
decay, reducing protein expression.
• Incorrect (B): Nonsense mutations do not reliably increase
translation; they terminate translation prematurely rather
than enhancing it.
• Incorrect (C): Promoter activity is independent of a coding-
region nonsense mutation.
• Incorrect (D): Trinucleotide repeat expansion is a distinct
mutational mechanism, not a direct consequence of a
single nonsense change.
Teaching Point
Nonsense mutations → premature stop codon → truncated
protein ± mRNA decay.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference — Ch. 1 — The Genome
Question Stem
A researcher comparing mutation rates between tissues notes
higher somatic mutation burden in rapidly dividing epithelium
than in terminally differentiated neurons. Which genomic factor
best explains this difference?
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
Reference — Ch. 1 — The Genome
Question Stem
A 58-year-old man with colorectal cancer shows a tumor with
high microsatellite instability (MSI-high). Which mechanism
best explains why MSI-high tumors accumulate frameshift
mutations in repetitive DNA tracts?
A. Defective nucleotide excision repair leading to thymine dimer
persistence
B. Germline TP53 point mutation causing global genomic
instability
,C. Defective DNA mismatch repair allowing replication slippage
errors to persist
D. Increased homologous recombination that creates repetitive-
sequence expansions
Correct Answer
C
Rationales
• Correct (C): DNA mismatch repair corrects
insertion/deletion loops that occur at repetitive
(microsatellite) sequences during replication; loss of
mismatch repair permits slippage errors to persist,
producing microsatellite instability and frameshift
mutations.
• Incorrect (A): Nucleotide excision repair removes bulky
helix-distorting lesions (e.g., thymine dimers), not
replication slippage at microsatellites.
• Incorrect (B): TP53 mutations cause impaired DNA damage
response but do not specifically cause microsatellite
slippage—the hallmark of MSI is defective mismatch repair.
• Incorrect (D): Homologous recombination repairs double-
strand breaks and does not increase small
insertion/deletion errors at microsatellites.
Teaching Point
Mismatch repair deficiency → unrepaired replication slippage
→ microsatellite instability.
,Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference — Ch. 1 — The Genome
Question Stem
A young adult presents with frequent bacterial infections and is
found to have a nonsense mutation early in a gene required for
innate immune signaling. Which consequence at the molecular
level most directly follows a premature stop (nonsense)
mutation?
A. Production of a truncated polypeptide and possible
nonsense-mediated mRNA decay
B. Increased translation efficiency due to alternative start codon
usage
C. Enhanced promoter activity raising transcription of the
mutant allele
D. Expansion of trinucleotide repeats in the affected gene
Correct Answer
A
Rationales
• Correct (A): Nonsense mutations introduce premature
stop codons that produce truncated proteins; often mRNAs
, with premature stops are targeted by nonsense-mediated
decay, reducing protein expression.
• Incorrect (B): Nonsense mutations do not reliably increase
translation; they terminate translation prematurely rather
than enhancing it.
• Incorrect (C): Promoter activity is independent of a coding-
region nonsense mutation.
• Incorrect (D): Trinucleotide repeat expansion is a distinct
mutational mechanism, not a direct consequence of a
single nonsense change.
Teaching Point
Nonsense mutations → premature stop codon → truncated
protein ± mRNA decay.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference — Ch. 1 — The Genome
Question Stem
A researcher comparing mutation rates between tissues notes
higher somatic mutation burden in rapidly dividing epithelium
than in terminally differentiated neurons. Which genomic factor
best explains this difference?
