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 1 — The Genome
Stem: A neonate is born with severe developmental delay.
Genetic testing shows a homozygous point mutation that
substitutes a hydrophobic residue in a core region of an
enzyme, leading to early degradation of the protein. Which
cellular process most likely recognizes and targets this
abnormal protein for rapid destruction?
A. Autophagy–lysosomal pathway
B. Ubiquitin–proteasome pathway
C. Endoplasmic reticulum–associated degradation (ERAD) via
lysosomes
D. Chaperone-mediated refolding in the Golgi apparatus
Correct Answer: B
Rationales:
, • Correct (B): The ubiquitin–proteasome system selectively
tags misfolded or abnormal cytosolic and nuclear proteins
for proteasomal degradation; point mutations that
destabilize proteins commonly lead to ubiquitination and
proteasomal destruction.
• (A) Autophagy–lysosomal pathway primarily degrades
long-lived proteins, organelles, and aggregates, not rapidly
degraded soluble misfolded proteins.
• (C) ERAD targets misfolded proteins in the ER for
retrotranslocation and proteasomal degradation rather
than lysosomal degradation.
• (D) Chaperone-mediated refolding occurs in the
cytosol/ER; the Golgi is not the site of chaperone-
mediated refolding.
Teaching Point: Misfolded soluble proteins are usually
eliminated by the ubiquitin–proteasome system.
Citation: Robbins & Cotran, 10th ed., Chap. 1, “The Genome” /
protein quality control.
2 — The Genome
Stem: A 45-year-old patient has a tumor with defective
mismatch repair (MMR) proteins. Which genomic consequence
best explains the tumor’s high rate of frameshift mutations in
microsatellite regions?
A. Failure to repair double-strand breaks by nonhomologous
,end joining
B. Inability to correct base–base mismatches and insertion–
deletion loops during replication
C. Defective homologous recombination leading to
chromosomal translocations
D. Increased deamination of 5-methylcytosine to thymine
Correct Answer: B
Rationales:
• Correct (B): MMR proteins correct replication errors such
as base–base mismatches and small insertion–deletion
loops; MMR deficiency produces microsatellite instability
and frameshift mutations.
• (A) Nonhomologous end joining repairs double-strand
breaks and is unrelated to microsatellite frameshifts.
• (C) Homologous recombination defects affect double-
strand break repair, causing large chromosomal changes,
not specifically microsatellite instability.
• (D) Deamination of 5-methylcytosine causes point
mutations (C→T), not the hallmark microsatellite
frameshifts of MMR loss.
Teaching Point: Defective MMR causes microsatellite instability
from unrepaired replication slippage.
Citation: Robbins & Cotran, 10th ed., Chap. 1, “The Genome” /
DNA repair mechanisms.
, 3 — Cellular Housekeeping
Stem: A pharmacologic agent increases autophagic flux in
hepatocytes. Which cellular effect is most consistent with
increased macroautophagy?
A. Selective ubiquitination and proteasomal degradation of
short-lived proteins
B. Formation of double-membrane autophagosomes that fuse
with lysosomes to degrade organelles
C. Direct lysosomal import of individual cytosolic proteins via
LAMP2A receptors
D. Increased exocytosis of lysosomal enzymes into the
extracellular matrix
Correct Answer: B
Rationales:
• Correct (B): Macroautophagy involves formation of
double-membrane autophagosomes that sequester
cytoplasmic contents and fuse with lysosomes for
degradation.
• (A) Ubiquitin–proteasome degradation is distinct from
macroautophagy and handles short-lived proteins.
• (C) Chaperone-mediated autophagy imports specific
proteins into lysosomes via receptors like LAMP2A, not
macroautophagy.
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter 1 — The Genome
Stem: A neonate is born with severe developmental delay.
Genetic testing shows a homozygous point mutation that
substitutes a hydrophobic residue in a core region of an
enzyme, leading to early degradation of the protein. Which
cellular process most likely recognizes and targets this
abnormal protein for rapid destruction?
A. Autophagy–lysosomal pathway
B. Ubiquitin–proteasome pathway
C. Endoplasmic reticulum–associated degradation (ERAD) via
lysosomes
D. Chaperone-mediated refolding in the Golgi apparatus
Correct Answer: B
Rationales:
, • Correct (B): The ubiquitin–proteasome system selectively
tags misfolded or abnormal cytosolic and nuclear proteins
for proteasomal degradation; point mutations that
destabilize proteins commonly lead to ubiquitination and
proteasomal destruction.
• (A) Autophagy–lysosomal pathway primarily degrades
long-lived proteins, organelles, and aggregates, not rapidly
degraded soluble misfolded proteins.
• (C) ERAD targets misfolded proteins in the ER for
retrotranslocation and proteasomal degradation rather
than lysosomal degradation.
• (D) Chaperone-mediated refolding occurs in the
cytosol/ER; the Golgi is not the site of chaperone-
mediated refolding.
Teaching Point: Misfolded soluble proteins are usually
eliminated by the ubiquitin–proteasome system.
Citation: Robbins & Cotran, 10th ed., Chap. 1, “The Genome” /
protein quality control.
2 — The Genome
Stem: A 45-year-old patient has a tumor with defective
mismatch repair (MMR) proteins. Which genomic consequence
best explains the tumor’s high rate of frameshift mutations in
microsatellite regions?
A. Failure to repair double-strand breaks by nonhomologous
,end joining
B. Inability to correct base–base mismatches and insertion–
deletion loops during replication
C. Defective homologous recombination leading to
chromosomal translocations
D. Increased deamination of 5-methylcytosine to thymine
Correct Answer: B
Rationales:
• Correct (B): MMR proteins correct replication errors such
as base–base mismatches and small insertion–deletion
loops; MMR deficiency produces microsatellite instability
and frameshift mutations.
• (A) Nonhomologous end joining repairs double-strand
breaks and is unrelated to microsatellite frameshifts.
• (C) Homologous recombination defects affect double-
strand break repair, causing large chromosomal changes,
not specifically microsatellite instability.
• (D) Deamination of 5-methylcytosine causes point
mutations (C→T), not the hallmark microsatellite
frameshifts of MMR loss.
Teaching Point: Defective MMR causes microsatellite instability
from unrepaired replication slippage.
Citation: Robbins & Cotran, 10th ed., Chap. 1, “The Genome” /
DNA repair mechanisms.
, 3 — Cellular Housekeeping
Stem: A pharmacologic agent increases autophagic flux in
hepatocytes. Which cellular effect is most consistent with
increased macroautophagy?
A. Selective ubiquitination and proteasomal degradation of
short-lived proteins
B. Formation of double-membrane autophagosomes that fuse
with lysosomes to degrade organelles
C. Direct lysosomal import of individual cytosolic proteins via
LAMP2A receptors
D. Increased exocytosis of lysosomal enzymes into the
extracellular matrix
Correct Answer: B
Rationales:
• Correct (B): Macroautophagy involves formation of
double-membrane autophagosomes that sequester
cytoplasmic contents and fuse with lysosomes for
degradation.
• (A) Ubiquitin–proteasome degradation is distinct from
macroautophagy and handles short-lived proteins.
• (C) Chaperone-mediated autophagy imports specific
proteins into lysosomes via receptors like LAMP2A, not
macroautophagy.
