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 28-year-old woman with a family history of early-onset breast
cancer has a variant detected in a tumor-suppressor gene that
reduces protein function but does not eliminate it. Which
cellular consequence best explains why partial loss of function
raises her cancer risk?
Options
A. Haploinsufficiency leading to inadequate tumor suppression.
B. Dominant-negative mutation causing increased oncogene
,activity.
C. Gain-of-function effect producing constitutive growth
signaling.
D. Somatic hypermutation increasing immune recognition.
Correct Answer
A
Rationales
• Correct (A): Haploinsufficiency occurs when a single
functional allele produces insufficient tumor-suppressor
protein to maintain normal control of proliferation,
increasing cancer risk. This fits the scenario of reduced —
but not absent — protein function.
• Incorrect (B): Dominant-negative mutations typically
involve an altered protein that interferes with the wild-
type protein’s function; the stem implies reduced function
rather than interference.
• Incorrect (C): Gain-of-function mutations are characteristic
of oncogenes, not loss-of-function changes in tumor
suppressors.
• Incorrect (D): Somatic hypermutation is an immune
process in lymphocytes and does not explain inherited
tumor-suppressor reduction.
Teaching Point
Haploinsufficiency: one allele’s reduced function can permit
tumor formation.
,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 newborn screening reveals a pathogenic mitochondrial DNA
mutation that impairs complex I function. Which clinical feature
is most plausibly related to this defect?
Options
A. Lactic acidosis and exercise intolerance.
B. Severe neutropenia due to marrow suppression.
C. Hypercoagulability with thrombosis.
D. Isolated prolonged prothrombin time.
Correct Answer
A
Rationales
• Correct (A): Impaired mitochondrial oxidative
phosphorylation forces reliance on anaerobic glycolysis,
producing lactic acidosis and causing tissues with high
energy demand (muscle) to show exercise intolerance.
, • Incorrect (B): Neutropenia from marrow suppression is not
a direct consequence of complex I mitochondrial defects.
• Incorrect (C): Hypercoagulability is not a primary
manifestation of mitochondrial respiratory chain defects.
• Incorrect (D): Prolongation of prothrombin time reflects
hepatic synthetic dysfunction or vitamin K deficiency, not a
primary mitochondrial complex I defect.
Teaching Point
Mitochondrial OXPHOS defects → impaired ATP → lactic
acidosis and muscle intolerance.
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 tumor shows extensive genomic instability and chromosomal
aneuploidy. Which defect in genomic maintenance most
directly explains this phenotype?
Options
A. Impaired DNA repair of double-strand breaks.
B. Excessive base excision repair activity.
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 28-year-old woman with a family history of early-onset breast
cancer has a variant detected in a tumor-suppressor gene that
reduces protein function but does not eliminate it. Which
cellular consequence best explains why partial loss of function
raises her cancer risk?
Options
A. Haploinsufficiency leading to inadequate tumor suppression.
B. Dominant-negative mutation causing increased oncogene
,activity.
C. Gain-of-function effect producing constitutive growth
signaling.
D. Somatic hypermutation increasing immune recognition.
Correct Answer
A
Rationales
• Correct (A): Haploinsufficiency occurs when a single
functional allele produces insufficient tumor-suppressor
protein to maintain normal control of proliferation,
increasing cancer risk. This fits the scenario of reduced —
but not absent — protein function.
• Incorrect (B): Dominant-negative mutations typically
involve an altered protein that interferes with the wild-
type protein’s function; the stem implies reduced function
rather than interference.
• Incorrect (C): Gain-of-function mutations are characteristic
of oncogenes, not loss-of-function changes in tumor
suppressors.
• Incorrect (D): Somatic hypermutation is an immune
process in lymphocytes and does not explain inherited
tumor-suppressor reduction.
Teaching Point
Haploinsufficiency: one allele’s reduced function can permit
tumor formation.
,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 newborn screening reveals a pathogenic mitochondrial DNA
mutation that impairs complex I function. Which clinical feature
is most plausibly related to this defect?
Options
A. Lactic acidosis and exercise intolerance.
B. Severe neutropenia due to marrow suppression.
C. Hypercoagulability with thrombosis.
D. Isolated prolonged prothrombin time.
Correct Answer
A
Rationales
• Correct (A): Impaired mitochondrial oxidative
phosphorylation forces reliance on anaerobic glycolysis,
producing lactic acidosis and causing tissues with high
energy demand (muscle) to show exercise intolerance.
, • Incorrect (B): Neutropenia from marrow suppression is not
a direct consequence of complex I mitochondrial defects.
• Incorrect (C): Hypercoagulability is not a primary
manifestation of mitochondrial respiratory chain defects.
• Incorrect (D): Prolongation of prothrombin time reflects
hepatic synthetic dysfunction or vitamin K deficiency, not a
primary mitochondrial complex I defect.
Teaching Point
Mitochondrial OXPHOS defects → impaired ATP → lactic
acidosis and muscle intolerance.
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 tumor shows extensive genomic instability and chromosomal
aneuploidy. Which defect in genomic maintenance most
directly explains this phenotype?
Options
A. Impaired DNA repair of double-strand breaks.
B. Excessive base excision repair activity.
