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 47-year-old patient’s tumor sequencing shows a loss-of-
function mutation in a DNA repair gene causing deficient repair
of single-strand DNA breaks. Which downstream consequence
best explains increased mutation accumulation in the tumor?
A. Increased error-free homologous recombination during S
phase
,B. Accumulation of unrepaired lesions leading to replication
fork collapse and double-strand breaks
C. Enhanced mismatch repair activity correcting replication
errors
D. Global upregulation of transcription-coupled repair
preventing mutations
Correct Answer
B
Rationales
• Correct (B): Defective single-strand break repair permits
lesions to persist; during DNA replication these unrepaired
lesions cause replication fork collapse producing double-
strand breaks, increasing mutation burden.
• Incorrect (A): Homologous recombination repairs double-
strand breaks and is not increased by failure to repair
single-strand breaks; this option describes an error-free
pathway that would reduce mutations, not increase them.
• Incorrect (C): Mismatch repair corrects replication
mismatches; loss of single-strand break repair does not
enhance mismatch repair.
• Incorrect (D): Transcription-coupled repair addresses
lesions on transcribed strands; global upregulation would
not explain increased mutation accumulation from
unrepaired single-strand breaks.
,Teaching Point
Unrepaired single-strand lesions → replication fork collapse →
double-strand breaks → genomic instability.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — The Genome
Question Stem
A newborn screening identifies a pathogenic variant that
shortens telomeres in hematopoietic stem cells. Which clinical
consequence is most directly explained by telomere shortening
in these stem cells?
A. Increased capacity for unlimited proliferation and
tumorigenesis
B. Stem cell senescence leading to bone marrow failure and
cytopenias
C. Enhanced DNA repair efficiency in progenitor cells
D. Permanent activation of telomerase in all somatic cells
Correct Answer
B
Rationales
, • Correct (B): Telomere shortening triggers replicative
senescence of stem cells, reducing regenerative capacity of
hematopoietic tissues and leading to bone marrow failure
and cytopenias.
• Incorrect (A): Unlimited proliferation is associated with
telomerase activation, not telomere shortening.
• Incorrect (C): Telomere shortening does not enhance DNA
repair; it induces DNA damage signaling and senescence.
• Incorrect (D): Shortened telomeres do not cause universal
telomerase activation; telomerase activation is a separate
event often seen in cancer.
Teaching Point
Telomere shortening → stem cell senescence → decreased
tissue regeneration.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference
Ch. 1 — Cellular Housekeeping
Question Stem
A patient with a lysosomal storage disease accumulates
undegraded substrates in macrophages. Which cellular process
is directly impaired and explains this accumulation?
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
Reference
Ch. 1 — The Genome
Question Stem
A 47-year-old patient’s tumor sequencing shows a loss-of-
function mutation in a DNA repair gene causing deficient repair
of single-strand DNA breaks. Which downstream consequence
best explains increased mutation accumulation in the tumor?
A. Increased error-free homologous recombination during S
phase
,B. Accumulation of unrepaired lesions leading to replication
fork collapse and double-strand breaks
C. Enhanced mismatch repair activity correcting replication
errors
D. Global upregulation of transcription-coupled repair
preventing mutations
Correct Answer
B
Rationales
• Correct (B): Defective single-strand break repair permits
lesions to persist; during DNA replication these unrepaired
lesions cause replication fork collapse producing double-
strand breaks, increasing mutation burden.
• Incorrect (A): Homologous recombination repairs double-
strand breaks and is not increased by failure to repair
single-strand breaks; this option describes an error-free
pathway that would reduce mutations, not increase them.
• Incorrect (C): Mismatch repair corrects replication
mismatches; loss of single-strand break repair does not
enhance mismatch repair.
• Incorrect (D): Transcription-coupled repair addresses
lesions on transcribed strands; global upregulation would
not explain increased mutation accumulation from
unrepaired single-strand breaks.
,Teaching Point
Unrepaired single-strand lesions → replication fork collapse →
double-strand breaks → genomic instability.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — The Genome
Question Stem
A newborn screening identifies a pathogenic variant that
shortens telomeres in hematopoietic stem cells. Which clinical
consequence is most directly explained by telomere shortening
in these stem cells?
A. Increased capacity for unlimited proliferation and
tumorigenesis
B. Stem cell senescence leading to bone marrow failure and
cytopenias
C. Enhanced DNA repair efficiency in progenitor cells
D. Permanent activation of telomerase in all somatic cells
Correct Answer
B
Rationales
, • Correct (B): Telomere shortening triggers replicative
senescence of stem cells, reducing regenerative capacity of
hematopoietic tissues and leading to bone marrow failure
and cytopenias.
• Incorrect (A): Unlimited proliferation is associated with
telomerase activation, not telomere shortening.
• Incorrect (C): Telomere shortening does not enhance DNA
repair; it induces DNA damage signaling and senescence.
• Incorrect (D): Shortened telomeres do not cause universal
telomerase activation; telomerase activation is a separate
event often seen in cancer.
Teaching Point
Telomere shortening → stem cell senescence → decreased
tissue regeneration.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference
Ch. 1 — Cellular Housekeeping
Question Stem
A patient with a lysosomal storage disease accumulates
undegraded substrates in macrophages. Which cellular process
is directly impaired and explains this accumulation?
