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 45-year-old woman’s tumor demonstrates microsatellite
instability (MSI). Which cellular defect most likely explains MSI
and contributes to the tumor’s mutational burden?
Options
A. Defective nucleotide excision repair of bulky adducts
,B. Impaired mismatch repair (MMR) leading to failure to correct
replication errors
C. Loss of homologous recombination for double-strand break
repair
D. Defective base excision repair of oxidative lesions
Correct Answer
B
Rationales
• Correct (B): Microsatellite instability arises from defects in
the DNA mismatch repair system, which normally corrects
base–base mismatches and insertion–deletion loops
during replication; loss increases small repeat region
mutations.
• Incorrect (A): Nucleotide excision repair removes bulky
helix-distorting lesions (e.g., UV adducts) and is not the
principal cause of MSI.
• Incorrect (C): Homologous recombination repairs double-
strand breaks; its loss causes chromosomal instability
rather than MSI.
• Incorrect (D): Base excision repair fixes small
oxidative/base lesions; failure here produces point
mutations but not characteristic MSI.
Teaching Point
MMR defects cause microsatellite instability by failing to correct
replication errors.
,Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2)
Reference
Ch. 1 — The Genome
Question Stem
A patient with a familial cancer syndrome has a germline
mutation in a tumor suppressor that impairs DNA damage–
induced cell-cycle arrest. Which mechanism best explains how
loss of this gene increases cancer risk?
Options
A. Increased activity of telomerase, preventing senescence
B. Failure to arrest the cell cycle for DNA repair, allowing
propagation of mutations
C. Upregulation of proteasomal degradation of cyclins
D. Enhanced mismatch repair fidelity leading to microsatellite
stability
Correct Answer
B
Rationales
• Correct (B): Tumor suppressors that mediate DNA damage
checkpoints prevent replication of damaged DNA; loss
, allows cells to continue dividing with mutations, increasing
oncogenesis.
• Incorrect (A): Telomerase activation promotes replicative
immortality but is a separate mechanism; germline
checkpoint loss does not directly increase telomerase.
• Incorrect (C): Increased proteasomal degradation of cyclins
would reduce proliferation, not increase cancer risk.
• Incorrect (D): Enhanced mismatch repair would decrease
mutation accumulation, lowering cancer risk.
Teaching Point
Checkpoint loss permits replication of damaged DNA,
promoting mutation accumulation and cancer.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3)
Reference
Ch. 1 — The Genome
Question Stem
A tumor sequencing panel shows a high tumor mutational
burden with numerous single-nucleotide substitutions caused
by reactive oxygen species (ROS). Which genomic maintenance
process is primarily responsible for repairing oxidative base
damage?
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
Reference
Ch. 1 — The Genome
Question Stem
A 45-year-old woman’s tumor demonstrates microsatellite
instability (MSI). Which cellular defect most likely explains MSI
and contributes to the tumor’s mutational burden?
Options
A. Defective nucleotide excision repair of bulky adducts
,B. Impaired mismatch repair (MMR) leading to failure to correct
replication errors
C. Loss of homologous recombination for double-strand break
repair
D. Defective base excision repair of oxidative lesions
Correct Answer
B
Rationales
• Correct (B): Microsatellite instability arises from defects in
the DNA mismatch repair system, which normally corrects
base–base mismatches and insertion–deletion loops
during replication; loss increases small repeat region
mutations.
• Incorrect (A): Nucleotide excision repair removes bulky
helix-distorting lesions (e.g., UV adducts) and is not the
principal cause of MSI.
• Incorrect (C): Homologous recombination repairs double-
strand breaks; its loss causes chromosomal instability
rather than MSI.
• Incorrect (D): Base excision repair fixes small
oxidative/base lesions; failure here produces point
mutations but not characteristic MSI.
Teaching Point
MMR defects cause microsatellite instability by failing to correct
replication errors.
,Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2)
Reference
Ch. 1 — The Genome
Question Stem
A patient with a familial cancer syndrome has a germline
mutation in a tumor suppressor that impairs DNA damage–
induced cell-cycle arrest. Which mechanism best explains how
loss of this gene increases cancer risk?
Options
A. Increased activity of telomerase, preventing senescence
B. Failure to arrest the cell cycle for DNA repair, allowing
propagation of mutations
C. Upregulation of proteasomal degradation of cyclins
D. Enhanced mismatch repair fidelity leading to microsatellite
stability
Correct Answer
B
Rationales
• Correct (B): Tumor suppressors that mediate DNA damage
checkpoints prevent replication of damaged DNA; loss
, allows cells to continue dividing with mutations, increasing
oncogenesis.
• Incorrect (A): Telomerase activation promotes replicative
immortality but is a separate mechanism; germline
checkpoint loss does not directly increase telomerase.
• Incorrect (C): Increased proteasomal degradation of cyclins
would reduce proliferation, not increase cancer risk.
• Incorrect (D): Enhanced mismatch repair would decrease
mutation accumulation, lowering cancer risk.
Teaching Point
Checkpoint loss permits replication of damaged DNA,
promoting mutation accumulation and cancer.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3)
Reference
Ch. 1 — The Genome
Question Stem
A tumor sequencing panel shows a high tumor mutational
burden with numerous single-nucleotide substitutions caused
by reactive oxygen species (ROS). Which genomic maintenance
process is primarily responsible for repairing oxidative base
damage?
