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 28-year-old woman is found to carry a BRCA1 frameshift
mutation discovered on family screening. Which molecular
consequence most directly explains why a frameshift mutation
in BRCA1 increases cancer risk?
Options
A. Altered promoter methylation reduces BRCA1 transcription.
B. A single amino-acid substitution reduces BRCA1 binding to
DNA.
C. Premature stop codon produces truncated protein that
impairs DNA repair.
,D. Increased BRCA1 mRNA stability causes toxic protein
accumulation.
Correct Answer
C
Rationales
Correct: Frameshift mutations often shift the reading frame
producing premature stop codons and truncated proteins;
truncated BRCA1 cannot perform homologous recombination
DNA repair, increasing genomic instability.
A: Promoter methylation is an epigenetic mechanism, not a
direct consequence of a frameshift mutation.
B: A single amino-acid substitution describes a missense
change, not the typical outcome of a frameshift.
D: Frameshifts usually destabilize proteins; increased mRNA
stability is not the primary mechanism here.
Teaching Point
Frameshift → truncated repair protein → defective homologous
recombination.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2.
Reference — Ch. 1 — The Genome
,Question Stem
A neonate presents with multiple congenital anomalies. Genetic
testing reveals defective nucleotide excision repair (NER). Which
environmental exposure would most likely exacerbate DNA
damage in this patient?
Options
A. Ionizing radiation from X-rays.
B. Ultraviolet (UV) sunlight exposure.
C. Dietary folate deficiency.
D. Inhaled benzene exposure.
Correct Answer
B
Rationales
Correct: NER specifically removes UV-induced bulky lesions such
as thymine dimers; defective NER increases sensitivity to UV
light.
A: Ionizing radiation causes double-strand breaks handled by
other repair pathways (e.g., homologous recombination).
C: Folate deficiency affects nucleotide synthesis, not directly
NER of bulky adducts.
D: Benzene causes bone marrow toxicity and specific adducts;
NER is most relevant for UV photolesions.
Teaching Point
NER repairs UV-induced bulky DNA lesions like thymine dimers.
, Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3.
Reference — Ch. 1 — The Genome
Question Stem
A 45-year-old man has progressive neurologic decline due to
trinucleotide repeat expansion in a neuronal gene. Which
mechanism best explains anticipation (worsening in successive
generations) in this disorder?
Options
A. Somatic point mutations accumulate with age.
B. Repeat sequences expand during gametogenesis, increasing
toxicity.
C. Loss of heterozygosity results in early gene inactivation.
D. Epigenetic silencing increases across generations.
Correct Answer
B
Rationales
Correct: Trinucleotide repeat disorders show instability with
repeat expansions during gametogenesis; larger repeats often
produce earlier or more severe disease in offspring
(anticipation).
A: Somatic point mutations accumulating with age do not
account for generational worsening.
10TH EDITION
AUTHOR(S)VINAY KUMAR; ABUL K.
ABBAS; JON C. ASTER
TEST BANK
Reference — Ch. 1 — The Genome
Question Stem
A 28-year-old woman is found to carry a BRCA1 frameshift
mutation discovered on family screening. Which molecular
consequence most directly explains why a frameshift mutation
in BRCA1 increases cancer risk?
Options
A. Altered promoter methylation reduces BRCA1 transcription.
B. A single amino-acid substitution reduces BRCA1 binding to
DNA.
C. Premature stop codon produces truncated protein that
impairs DNA repair.
,D. Increased BRCA1 mRNA stability causes toxic protein
accumulation.
Correct Answer
C
Rationales
Correct: Frameshift mutations often shift the reading frame
producing premature stop codons and truncated proteins;
truncated BRCA1 cannot perform homologous recombination
DNA repair, increasing genomic instability.
A: Promoter methylation is an epigenetic mechanism, not a
direct consequence of a frameshift mutation.
B: A single amino-acid substitution describes a missense
change, not the typical outcome of a frameshift.
D: Frameshifts usually destabilize proteins; increased mRNA
stability is not the primary mechanism here.
Teaching Point
Frameshift → truncated repair protein → defective homologous
recombination.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2.
Reference — Ch. 1 — The Genome
,Question Stem
A neonate presents with multiple congenital anomalies. Genetic
testing reveals defective nucleotide excision repair (NER). Which
environmental exposure would most likely exacerbate DNA
damage in this patient?
Options
A. Ionizing radiation from X-rays.
B. Ultraviolet (UV) sunlight exposure.
C. Dietary folate deficiency.
D. Inhaled benzene exposure.
Correct Answer
B
Rationales
Correct: NER specifically removes UV-induced bulky lesions such
as thymine dimers; defective NER increases sensitivity to UV
light.
A: Ionizing radiation causes double-strand breaks handled by
other repair pathways (e.g., homologous recombination).
C: Folate deficiency affects nucleotide synthesis, not directly
NER of bulky adducts.
D: Benzene causes bone marrow toxicity and specific adducts;
NER is most relevant for UV photolesions.
Teaching Point
NER repairs UV-induced bulky DNA lesions like thymine dimers.
, Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3.
Reference — Ch. 1 — The Genome
Question Stem
A 45-year-old man has progressive neurologic decline due to
trinucleotide repeat expansion in a neuronal gene. Which
mechanism best explains anticipation (worsening in successive
generations) in this disorder?
Options
A. Somatic point mutations accumulate with age.
B. Repeat sequences expand during gametogenesis, increasing
toxicity.
C. Loss of heterozygosity results in early gene inactivation.
D. Epigenetic silencing increases across generations.
Correct Answer
B
Rationales
Correct: Trinucleotide repeat disorders show instability with
repeat expansions during gametogenesis; larger repeats often
produce earlier or more severe disease in offspring
(anticipation).
A: Somatic point mutations accumulating with age do not
account for generational worsening.
