Robbins Basic Pathology
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A 32-year-old woman has recurrent breast cancer at age 32
with a strong family history. Genetic testing reveals a
nonfunctional BRCA1 allele caused by a frameshift mutation.
Which cellular consequence best explains her markedly
increased breast cancer risk?
,Options
A. Increased error-prone translesion DNA synthesis during
replication
B. Loss of homologous recombination–mediated DNA repair
leading to accumulation of double-strand breaks
C. Upregulation of base excision repair causing hypermutability
D. Enhanced mismatch repair causing cell cycle arrest and
hyperplasia
Correct Answer
B
Rationales
Correct: BRCA1 is essential for homologous recombination
repair of double-strand DNA breaks; loss leads to accumulation
of unrepaired double-strand breaks and genomic instability that
promotes cancer. (Robbins describes BRCA1’s role in high-
fidelity repair.)
A. Translesion synthesis is a bypass mechanism and is not the
principal defect from BRCA1 loss; it does not explain double-
strand break accumulation.
C. Base excision repair fixes small base lesions; BRCA1 defects
do not cause its upregulation or hypermutability via this
pathway.
D. Mismatch repair defects (not BRCA1) cause microsatellite
instability; mismatch repair upregulation would not produce the
observed phenotype.
,Teaching Point
BRCA1 loss → defective homologous recombination → genomic
instability and cancer risk.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A patient’s tumor sequencing shows a recurrent C>T transition
at CpG dinucleotides. Which mechanism most likely produced
these mutations?
Options
A. Spontaneous deamination of 5-methylcytosine producing
thymine during DNA replication
B. Oxidation of guanine to 8-oxoguanine leading to mispairing
with adenine
C. UV radiation causing thymine dimer formation and
replication stalling
D. Insertion of apurinic sites during base excision repair
Correct Answer
A
, Rationales
Correct: Methylated cytosines at CpG sites can spontaneously
deaminate to thymine, producing C→T transitions commonly
seen in cancers; Robbins highlights this as a frequent
endogenous mutational mechanism.
B. Oxidative damage to guanine causes G→T transversions (8-
oxoguanine), not C→T transitions.
C. UV-induced thymine dimers produce characteristic
pyrimidine dimers, especially CC→TT tandem mutations, not
isolated CpG C→T changes.
D. Apurinic/apyrimidinic sites are loss of bases, not the specific
C→T transition from deamination.
Teaching Point
5-methylcytosine deamination at CpG → common endogenous
C→T mutation hotspot.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A new chemotherapeutic agent causes inhibition of nucleotide
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A 32-year-old woman has recurrent breast cancer at age 32
with a strong family history. Genetic testing reveals a
nonfunctional BRCA1 allele caused by a frameshift mutation.
Which cellular consequence best explains her markedly
increased breast cancer risk?
,Options
A. Increased error-prone translesion DNA synthesis during
replication
B. Loss of homologous recombination–mediated DNA repair
leading to accumulation of double-strand breaks
C. Upregulation of base excision repair causing hypermutability
D. Enhanced mismatch repair causing cell cycle arrest and
hyperplasia
Correct Answer
B
Rationales
Correct: BRCA1 is essential for homologous recombination
repair of double-strand DNA breaks; loss leads to accumulation
of unrepaired double-strand breaks and genomic instability that
promotes cancer. (Robbins describes BRCA1’s role in high-
fidelity repair.)
A. Translesion synthesis is a bypass mechanism and is not the
principal defect from BRCA1 loss; it does not explain double-
strand break accumulation.
C. Base excision repair fixes small base lesions; BRCA1 defects
do not cause its upregulation or hypermutability via this
pathway.
D. Mismatch repair defects (not BRCA1) cause microsatellite
instability; mismatch repair upregulation would not produce the
observed phenotype.
,Teaching Point
BRCA1 loss → defective homologous recombination → genomic
instability and cancer risk.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A patient’s tumor sequencing shows a recurrent C>T transition
at CpG dinucleotides. Which mechanism most likely produced
these mutations?
Options
A. Spontaneous deamination of 5-methylcytosine producing
thymine during DNA replication
B. Oxidation of guanine to 8-oxoguanine leading to mispairing
with adenine
C. UV radiation causing thymine dimer formation and
replication stalling
D. Insertion of apurinic sites during base excision repair
Correct Answer
A
, Rationales
Correct: Methylated cytosines at CpG sites can spontaneously
deaminate to thymine, producing C→T transitions commonly
seen in cancers; Robbins highlights this as a frequent
endogenous mutational mechanism.
B. Oxidative damage to guanine causes G→T transversions (8-
oxoguanine), not C→T transitions.
C. UV-induced thymine dimers produce characteristic
pyrimidine dimers, especially CC→TT tandem mutations, not
isolated CpG C→T changes.
D. Apurinic/apyrimidinic sites are loss of bases, not the specific
C→T transition from deamination.
Teaching Point
5-methylcytosine deamination at CpG → common endogenous
C→T mutation hotspot.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A new chemotherapeutic agent causes inhibition of nucleotide
