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 42-year-old woman with a strong family history of early
breast cancer is found to carry a pathogenic BRCA1 frameshift
mutation. Which cellular consequence best explains her
increased cancer risk?
Options
A. Increased mitochondrial ROS production leading to DNA
,strand breaks
B. Impaired homologous recombination repair of double-strand
DNA breaks
C. Enhanced mismatch repair causing excessive apoptosis of
stem cells
D. Upregulated base excision repair producing mutagenic
intermediates
Correct Answer
B
Rationales
Correct (B): BRCA1 is pivotal for homologous recombination
repair of DNA double-strand breaks; loss impairs accurate repair
increasing genomic instability and cancer risk.
Incorrect (A): Mitochondrial ROS can cause DNA damage but
BRCA1 mutation primarily impairs nuclear double-strand break
repair, not ROS generation.
Incorrect (C): Mismatch repair corrects replication errors; its
enhancement would not explain increased cancer risk via
BRCA1.
Incorrect (D): Base excision repair fixes single-base lesions;
BRCA1 defects do not cause upregulation of this pathway
producing mutagenic intermediates.
Teaching Point
BRCA1 loss → defective homologous recombination → genomic
instability → cancer.
,Citation (simplified APA)
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — Cellular Housekeeping
Question Stem
A patient presents with progressive neurodegeneration
characterized by accumulation of ubiquitin-positive
intraneuronal inclusions. Which defect most directly explains
these inclusions?
Options
A. Failure of lysosomal acidification during autophagy
B. Dysfunctional ubiquitin-proteasome system leading to
reduced protein degradation
C. Increased exocytotic secretion of misfolded proteins
D. Enhanced mitochondrial biogenesis increasing protein
turnover demands
Correct Answer
B
Rationales
Correct (B): The ubiquitin-proteasome pathway degrades
misfolded cytosolic and short-lived proteins; its dysfunction
produces ubiquitin-positive inclusions.
Incorrect (A): Lysosomal/autophagic dysfunction causes
, accumulation of autophagic vacuoles, often p62 positive, but
ubiquitin-proteasome failure is classically linked to ubiquitin-
positive inclusions.
Incorrect (C): Exocytosis would decrease intracellular
accumulation rather than cause inclusion formation.
Incorrect (D): Increased mitochondrial biogenesis does not
directly lead to ubiquitin-positive protein inclusions.
Teaching Point
Proteasome dysfunction → accumulation of ubiquitinated
misfolded proteins.
Citation (simplified APA)
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference
Ch. 1 — Cellular Metabolism and Mitochondrial Function
Question Stem
A trauma patient becomes hypotensive and develops
widespread cellular swelling and lactic acidosis despite fluid
resuscitation. Which mitochondrial event best explains the shift
to anaerobic metabolism and cellular swelling?
Options
A. Increased mitochondrial biogenesis and ATP overproduction
B. Opening of the mitochondrial permeability transition pore
causing loss of ATP production
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
Reference
Ch. 1 — The Genome
Question Stem
A 42-year-old woman with a strong family history of early
breast cancer is found to carry a pathogenic BRCA1 frameshift
mutation. Which cellular consequence best explains her
increased cancer risk?
Options
A. Increased mitochondrial ROS production leading to DNA
,strand breaks
B. Impaired homologous recombination repair of double-strand
DNA breaks
C. Enhanced mismatch repair causing excessive apoptosis of
stem cells
D. Upregulated base excision repair producing mutagenic
intermediates
Correct Answer
B
Rationales
Correct (B): BRCA1 is pivotal for homologous recombination
repair of DNA double-strand breaks; loss impairs accurate repair
increasing genomic instability and cancer risk.
Incorrect (A): Mitochondrial ROS can cause DNA damage but
BRCA1 mutation primarily impairs nuclear double-strand break
repair, not ROS generation.
Incorrect (C): Mismatch repair corrects replication errors; its
enhancement would not explain increased cancer risk via
BRCA1.
Incorrect (D): Base excision repair fixes single-base lesions;
BRCA1 defects do not cause upregulation of this pathway
producing mutagenic intermediates.
Teaching Point
BRCA1 loss → defective homologous recombination → genomic
instability → cancer.
,Citation (simplified APA)
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — Cellular Housekeeping
Question Stem
A patient presents with progressive neurodegeneration
characterized by accumulation of ubiquitin-positive
intraneuronal inclusions. Which defect most directly explains
these inclusions?
Options
A. Failure of lysosomal acidification during autophagy
B. Dysfunctional ubiquitin-proteasome system leading to
reduced protein degradation
C. Increased exocytotic secretion of misfolded proteins
D. Enhanced mitochondrial biogenesis increasing protein
turnover demands
Correct Answer
B
Rationales
Correct (B): The ubiquitin-proteasome pathway degrades
misfolded cytosolic and short-lived proteins; its dysfunction
produces ubiquitin-positive inclusions.
Incorrect (A): Lysosomal/autophagic dysfunction causes
, accumulation of autophagic vacuoles, often p62 positive, but
ubiquitin-proteasome failure is classically linked to ubiquitin-
positive inclusions.
Incorrect (C): Exocytosis would decrease intracellular
accumulation rather than cause inclusion formation.
Incorrect (D): Increased mitochondrial biogenesis does not
directly lead to ubiquitin-positive protein inclusions.
Teaching Point
Proteasome dysfunction → accumulation of ubiquitinated
misfolded proteins.
Citation (simplified APA)
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference
Ch. 1 — Cellular Metabolism and Mitochondrial Function
Question Stem
A trauma patient becomes hypotensive and develops
widespread cellular swelling and lactic acidosis despite fluid
resuscitation. Which mitochondrial event best explains the shift
to anaerobic metabolism and cellular swelling?
Options
A. Increased mitochondrial biogenesis and ATP overproduction
B. Opening of the mitochondrial permeability transition pore
causing loss of ATP production
