Robbins & Cotran 10th Ed. Pathology Test Bank | Chapter-
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A 28-year-old woman has recurrent miscarriages. Genetic
testing of fetal tissue reveals multiple de novo single-base
substitutions in the developing embryo not present in parental
genomes. Which cellular process most likely failed in the
parental gametes leading to these mutations in offspring?
A. Base-excision DNA repair during S phase
B. Homologous recombination repair of double-strand breaks
C. DNA mismatch repair during post-replication proofreading
D. Nucleotide excision repair for bulky adducts
Answer: C
Rationale (Correct): DNA mismatch repair corrects replication
errors (single-base mismatches and small insertion-deletion
,loops) that occur during DNA replication. Failure in mismatch
repair in parental germ cells leads to accumulation of single-
base substitutions and microsatellite instability passed to
embryos.
Rationale (A): Base-excision repair fixes small, non-helix-
distorting base lesions (e.g., deaminated bases), not generalized
replication mismatches.
Rationale (B): Homologous recombination repairs double-
strand breaks and would cause larger chromosomal
abnormalities if defective.
Rationale (D): Nucleotide excision repair removes bulky helix-
distorting lesions (e.g., UV photoproducts), not typical single-
base replication mismatches.
Teaching Point: Mismatch repair corrects replication errors; its
failure increases single-base substitutions.
2
Chapter Reference – Chapter 1 — The Genome
Stem: A tumor is found to have an oncogenic point mutation in
a proto-oncogene that increases the protein’s activity. Which
type of mutation and genetic effect best describes this change?
A. Loss-of-function mutation; recessive at cellular level
B. Gain-of-function mutation; dominant at cellular level
C. Frameshift mutation; haploinsufficiency
D. Nonsense mutation; dominant-negative effect
Answer: B
,Rationale (Correct): Oncogenic point mutations that increase
proto-oncogene activity are gain-of-function and typically act
dominantly (one mutant allele suffices to promote growth).
Rationale (A): Loss-of-function mutations are usually recessive
and reduce protein activity; they do not explain increased
oncogene activity.
Rationale (C): Frameshift mutations disrupt reading frame and
typically lead to loss of function, not the activating change
described.
Rationale (D): Nonsense mutations truncate proteins and
usually produce loss of function or dominant-negative effects,
not an activating mutation increasing activity.
Teaching Point: Oncogenic point mutations often produce gain-
of-function, dominant-acting proto-oncogenes.
3
Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A 55-year-old man’s liver biopsy shows accumulation of
ubiquitinated, misfolded proteins in hepatocyte cytoplasm.
Which pathway is primarily responsible for degrading these
tagged cytosolic proteins?
A. Lysosomal autophagy (macroautophagy)
B. Proteasomal degradation via the ubiquitin–proteasome
system
C. Endoplasmic reticulum–associated degradation (ERAD)
delivering proteins to lysosomes
D. Phagocytosis by Kupffer cells
, Answer: B
Rationale (Correct): The ubiquitin–proteasome system targets
short-lived and misfolded cytosolic and nuclear proteins tagged
with ubiquitin for proteasomal degradation. Accumulation of
ubiquitinated proteins indicates proteasomal dysfunction.
Rationale (A): Macroautophagy degrades long-lived proteins
and organelles by delivering them to lysosomes, not primarily
ubiquitinated cytosolic proteins.
Rationale (C): ERAD targets misfolded proteins in the ER for
proteasomal degradation, not delivery to lysosomes primarily.
Rationale (D): Phagocytosis by Kupffer cells removes external
particles or dead cells, not intracellular ubiquitinated proteins.
Teaching Point: The ubiquitin–proteasome system clears
ubiquitinated cytosolic and nuclear proteins.
4
Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A patient with a genetic deficiency of lysosomal α-L-
iduronidase accumulates dermatan and heparan sulfates in
multiple tissues. Which cellular process is defective?
A. Autophagic sequestration of organelles
B. Phagosome–lysosome fusion in macrophages
C. Lysosomal hydrolysis of glycosaminoglycans
D. Proteasomal degradation of ubiquitinated proteins
Answer: C
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A 28-year-old woman has recurrent miscarriages. Genetic
testing of fetal tissue reveals multiple de novo single-base
substitutions in the developing embryo not present in parental
genomes. Which cellular process most likely failed in the
parental gametes leading to these mutations in offspring?
A. Base-excision DNA repair during S phase
B. Homologous recombination repair of double-strand breaks
C. DNA mismatch repair during post-replication proofreading
D. Nucleotide excision repair for bulky adducts
Answer: C
Rationale (Correct): DNA mismatch repair corrects replication
errors (single-base mismatches and small insertion-deletion
,loops) that occur during DNA replication. Failure in mismatch
repair in parental germ cells leads to accumulation of single-
base substitutions and microsatellite instability passed to
embryos.
Rationale (A): Base-excision repair fixes small, non-helix-
distorting base lesions (e.g., deaminated bases), not generalized
replication mismatches.
Rationale (B): Homologous recombination repairs double-
strand breaks and would cause larger chromosomal
abnormalities if defective.
Rationale (D): Nucleotide excision repair removes bulky helix-
distorting lesions (e.g., UV photoproducts), not typical single-
base replication mismatches.
Teaching Point: Mismatch repair corrects replication errors; its
failure increases single-base substitutions.
2
Chapter Reference – Chapter 1 — The Genome
Stem: A tumor is found to have an oncogenic point mutation in
a proto-oncogene that increases the protein’s activity. Which
type of mutation and genetic effect best describes this change?
A. Loss-of-function mutation; recessive at cellular level
B. Gain-of-function mutation; dominant at cellular level
C. Frameshift mutation; haploinsufficiency
D. Nonsense mutation; dominant-negative effect
Answer: B
,Rationale (Correct): Oncogenic point mutations that increase
proto-oncogene activity are gain-of-function and typically act
dominantly (one mutant allele suffices to promote growth).
Rationale (A): Loss-of-function mutations are usually recessive
and reduce protein activity; they do not explain increased
oncogene activity.
Rationale (C): Frameshift mutations disrupt reading frame and
typically lead to loss of function, not the activating change
described.
Rationale (D): Nonsense mutations truncate proteins and
usually produce loss of function or dominant-negative effects,
not an activating mutation increasing activity.
Teaching Point: Oncogenic point mutations often produce gain-
of-function, dominant-acting proto-oncogenes.
3
Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A 55-year-old man’s liver biopsy shows accumulation of
ubiquitinated, misfolded proteins in hepatocyte cytoplasm.
Which pathway is primarily responsible for degrading these
tagged cytosolic proteins?
A. Lysosomal autophagy (macroautophagy)
B. Proteasomal degradation via the ubiquitin–proteasome
system
C. Endoplasmic reticulum–associated degradation (ERAD)
delivering proteins to lysosomes
D. Phagocytosis by Kupffer cells
, Answer: B
Rationale (Correct): The ubiquitin–proteasome system targets
short-lived and misfolded cytosolic and nuclear proteins tagged
with ubiquitin for proteasomal degradation. Accumulation of
ubiquitinated proteins indicates proteasomal dysfunction.
Rationale (A): Macroautophagy degrades long-lived proteins
and organelles by delivering them to lysosomes, not primarily
ubiquitinated cytosolic proteins.
Rationale (C): ERAD targets misfolded proteins in the ER for
proteasomal degradation, not delivery to lysosomes primarily.
Rationale (D): Phagocytosis by Kupffer cells removes external
particles or dead cells, not intracellular ubiquitinated proteins.
Teaching Point: The ubiquitin–proteasome system clears
ubiquitinated cytosolic and nuclear proteins.
4
Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A patient with a genetic deficiency of lysosomal α-L-
iduronidase accumulates dermatan and heparan sulfates in
multiple tissues. Which cellular process is defective?
A. Autophagic sequestration of organelles
B. Phagosome–lysosome fusion in macrophages
C. Lysosomal hydrolysis of glycosaminoglycans
D. Proteasomal degradation of ubiquitinated proteins
Answer: C
