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 pregnant patient is found on prenatal
screening to carry a heterozygous mutation that produces
a dominant-negative transcription factor. Which cellular
consequence best explains how a dominant-negative
mutation typically impairs gene function?
, Options
A. Loss of one allele leads to 50% reduction in normal
protein levels.
B. Mutant protein interferes with assembly or function of
multimeric protein complexes.
C. The mutation increases transcription of the wild-type
allele by feedback activation.
D. Mutant mRNA is rapidly degraded by nonsense-
mediated decay, eliminating all protein.
Correct Answer
B
Rationales
• Correct (B): Dominant-negative mutations produce an
abnormal protein that disrupts multimeric complexes or
blocks normal protein function. This is a common
mechanism by which a mutant allele antagonizes the wild-
type product.
• Incorrect (A): A 50% reduction describes
haploinsufficiency, not dominant-negative interference
with multimeric complexes.
• Incorrect (C): Mutant proteins rarely upregulate the wild-
type allele; positive feedback of that sort is not the usual
dominant-negative mechanism.
,• Incorrect (D): Nonsense-mediated decay eliminates mRNA
from premature stop codons but does not describe
dominant-negative protein interference.
Teaching Point
Dominant-negative mutations make abnormal proteins
that poison multimeric complexes.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.).
Ch. 1.
2
Reference
Ch. 1 — The Genome
Question Stem
A tumor biopsy shows an oncogenic point mutation that
constitutively activates a GTPase. Which genomic
mechanism most directly explains how a single base
substitution can lock a signaling GTPase in its active state?
Options
A. Mutation eliminates guanine nucleotide exchange factor
(GEF) binding site, preventing activation.
B. Base change disrupts intrinsic GTPase activity,
preventing GTP hydrolysis and leaving the protein GTP-
bound.
C. Substitution causes rapid ubiquitin-mediated
, degradation of the GTPase.
D. The point mutation creates a novel splice site leading to
truncated protein.
Correct Answer
B
Rationales
• Correct (B): Oncogenic point mutations in small GTPases
often impair GTP hydrolysis, leaving them constitutively
GTP-bound and active, driving downstream signaling.
• Incorrect (A): Loss of GEF binding would reduce activation,
not cause constitutive activity.
• Incorrect (C): Degradation would lower protein activity;
oncogenic activation requires persistence, not degradation.
• Incorrect (D): Novel splice sites cause truncation;
constitutive activation of GTPases is typically from
impaired hydrolysis rather than truncation.
Teaching Point
Oncogenic GTPase mutations often impair GTP hydrolysis,
causing persistent activation.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.).
Ch. 1.
3
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 pregnant patient is found on prenatal
screening to carry a heterozygous mutation that produces
a dominant-negative transcription factor. Which cellular
consequence best explains how a dominant-negative
mutation typically impairs gene function?
, Options
A. Loss of one allele leads to 50% reduction in normal
protein levels.
B. Mutant protein interferes with assembly or function of
multimeric protein complexes.
C. The mutation increases transcription of the wild-type
allele by feedback activation.
D. Mutant mRNA is rapidly degraded by nonsense-
mediated decay, eliminating all protein.
Correct Answer
B
Rationales
• Correct (B): Dominant-negative mutations produce an
abnormal protein that disrupts multimeric complexes or
blocks normal protein function. This is a common
mechanism by which a mutant allele antagonizes the wild-
type product.
• Incorrect (A): A 50% reduction describes
haploinsufficiency, not dominant-negative interference
with multimeric complexes.
• Incorrect (C): Mutant proteins rarely upregulate the wild-
type allele; positive feedback of that sort is not the usual
dominant-negative mechanism.
,• Incorrect (D): Nonsense-mediated decay eliminates mRNA
from premature stop codons but does not describe
dominant-negative protein interference.
Teaching Point
Dominant-negative mutations make abnormal proteins
that poison multimeric complexes.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.).
Ch. 1.
2
Reference
Ch. 1 — The Genome
Question Stem
A tumor biopsy shows an oncogenic point mutation that
constitutively activates a GTPase. Which genomic
mechanism most directly explains how a single base
substitution can lock a signaling GTPase in its active state?
Options
A. Mutation eliminates guanine nucleotide exchange factor
(GEF) binding site, preventing activation.
B. Base change disrupts intrinsic GTPase activity,
preventing GTP hydrolysis and leaving the protein GTP-
bound.
C. Substitution causes rapid ubiquitin-mediated
, degradation of the GTPase.
D. The point mutation creates a novel splice site leading to
truncated protein.
Correct Answer
B
Rationales
• Correct (B): Oncogenic point mutations in small GTPases
often impair GTP hydrolysis, leaving them constitutively
GTP-bound and active, driving downstream signaling.
• Incorrect (A): Loss of GEF binding would reduce activation,
not cause constitutive activity.
• Incorrect (C): Degradation would lower protein activity;
oncogenic activation requires persistence, not degradation.
• Incorrect (D): Novel splice sites cause truncation;
constitutive activation of GTPases is typically from
impaired hydrolysis rather than truncation.
Teaching Point
Oncogenic GTPase mutations often impair GTP hydrolysis,
causing persistent activation.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.).
Ch. 1.
3
