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
Question 1
Chapter & Section: 1. The Genome
Question Stem: A research scientist is studying how identical
genetic sequences can lead to different cell types (e.g., a
hepatocyte vs. a neuron). Which mechanism best explains this
phenomenon by altering gene accessibility without changing
the DNA sequence itself?
Answer Options:
A) Accumulation of DNA point mutations
B) Epigenetic modifications, such as DNA methylation and
histone acetylation
C) Activation of DNA repair pathways like base excision repair
D) Variations in the mitochondrial genome
Correct Answer: B
Rationales:
, • Correct Answer (B): Epigenetic modifications regulate
gene expression by altering chromatin structure (e.g.,
methylation silences genes, acetylation opens chromatin),
allowing for cell-specific gene expression patterns from the
same genome. This is fundamental to cellular
differentiation.
• Incorrect A: Point mutations change the DNA sequence
itself and are not the primary mechanism for normal cell
differentiation.
• Incorrect C: DNA repair pathways maintain genomic
integrity but do not program cell-type-specific gene
expression.
• Incorrect D: The mitochondrial genome encodes energy-
related proteins and does not dictate nuclear gene
expression for cell identity.
Teaching Point: Epigenetics determines cell identity by
reversibly modifying DNA and histones to control gene
expression.
Citation: Chapter 1: The Genome
Question 2
Chapter & Section: 1. The Genome
Question Stem: A patient with a family history of cancer is
found to have a heterozygous germline mutation in a tumor
suppressor gene. According to the "two-hit" hypothesis, what
must occur in a cell for a neoplasm to develop?
,Answer Options:
A) The mutant allele must be amplified, leading to
overexpression.
B) The remaining wild-type allele must undergo a loss-of-
function mutation or deletion.
C) A proto-oncogene on a different chromosome must be
activated.
D) The mutant allele must be repaired via non-homologous end
joining.
Correct Answer: B
Rationales:
• Correct Answer (B): The "two-hit" hypothesis states that
both alleles of a tumor suppressor gene must be
inactivated for loss of growth inhibition. The first hit is the
inherited mutation; the second hit is an acquired somatic
mutation in the normal allele.
• Incorrect A: Amplification and overexpression are
mechanisms of oncogene activation, not tumor suppressor
gene inactivation.
• Incorrect C: While oncogene activation can cooperate, it is
not the "second hit" required for this specific tumor
suppressor gene.
• Incorrect D: Repair of the mutant allele would restore
function, not promote tumorigenesis.
Teaching Point: Tumor suppressor genes require biallelic
inactivation ("two hits") to lose their restraining influence
, on cell growth.
Citation: Chapter 1: The Genome
Question 3
Chapter & Section: 1. Cellular Housekeeping
Question Stem: A 2-year-old child presents with
neurodegeneration and hepatosplenomegaly. A biopsy reveals
undegraded sphingolipids accumulating within lysosomes. This
finding is most specific for a defect in which of the following
cellular systems?
Answer Options:
A) The ubiquitin-proteasome system
B) Mitochondrial oxidative phosphorylation
C) Lysosomal hydrolytic enzymes
D) Peroxisomal beta-oxidation enzymes
Correct Answer: C
Rationales:
• Correct Answer (C): Lysosomal storage diseases result
from deficiencies in specific lysosomal acid hydrolases,
leading to the accumulation of undegraded substrates
within the organelle, which disrupts cellular function.
• Incorrect A: The proteasome degrades ubiquitin-tagged
proteins, not complex lipids within lysosomes.
• Incorrect B: Mitochondrial defects impair energy
production but do not cause substrate accumulation in
lysosomes.
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Question 1
Chapter & Section: 1. The Genome
Question Stem: A research scientist is studying how identical
genetic sequences can lead to different cell types (e.g., a
hepatocyte vs. a neuron). Which mechanism best explains this
phenomenon by altering gene accessibility without changing
the DNA sequence itself?
Answer Options:
A) Accumulation of DNA point mutations
B) Epigenetic modifications, such as DNA methylation and
histone acetylation
C) Activation of DNA repair pathways like base excision repair
D) Variations in the mitochondrial genome
Correct Answer: B
Rationales:
, • Correct Answer (B): Epigenetic modifications regulate
gene expression by altering chromatin structure (e.g.,
methylation silences genes, acetylation opens chromatin),
allowing for cell-specific gene expression patterns from the
same genome. This is fundamental to cellular
differentiation.
• Incorrect A: Point mutations change the DNA sequence
itself and are not the primary mechanism for normal cell
differentiation.
• Incorrect C: DNA repair pathways maintain genomic
integrity but do not program cell-type-specific gene
expression.
• Incorrect D: The mitochondrial genome encodes energy-
related proteins and does not dictate nuclear gene
expression for cell identity.
Teaching Point: Epigenetics determines cell identity by
reversibly modifying DNA and histones to control gene
expression.
Citation: Chapter 1: The Genome
Question 2
Chapter & Section: 1. The Genome
Question Stem: A patient with a family history of cancer is
found to have a heterozygous germline mutation in a tumor
suppressor gene. According to the "two-hit" hypothesis, what
must occur in a cell for a neoplasm to develop?
,Answer Options:
A) The mutant allele must be amplified, leading to
overexpression.
B) The remaining wild-type allele must undergo a loss-of-
function mutation or deletion.
C) A proto-oncogene on a different chromosome must be
activated.
D) The mutant allele must be repaired via non-homologous end
joining.
Correct Answer: B
Rationales:
• Correct Answer (B): The "two-hit" hypothesis states that
both alleles of a tumor suppressor gene must be
inactivated for loss of growth inhibition. The first hit is the
inherited mutation; the second hit is an acquired somatic
mutation in the normal allele.
• Incorrect A: Amplification and overexpression are
mechanisms of oncogene activation, not tumor suppressor
gene inactivation.
• Incorrect C: While oncogene activation can cooperate, it is
not the "second hit" required for this specific tumor
suppressor gene.
• Incorrect D: Repair of the mutant allele would restore
function, not promote tumorigenesis.
Teaching Point: Tumor suppressor genes require biallelic
inactivation ("two hits") to lose their restraining influence
, on cell growth.
Citation: Chapter 1: The Genome
Question 3
Chapter & Section: 1. Cellular Housekeeping
Question Stem: A 2-year-old child presents with
neurodegeneration and hepatosplenomegaly. A biopsy reveals
undegraded sphingolipids accumulating within lysosomes. This
finding is most specific for a defect in which of the following
cellular systems?
Answer Options:
A) The ubiquitin-proteasome system
B) Mitochondrial oxidative phosphorylation
C) Lysosomal hydrolytic enzymes
D) Peroxisomal beta-oxidation enzymes
Correct Answer: C
Rationales:
• Correct Answer (C): Lysosomal storage diseases result
from deficiencies in specific lysosomal acid hydrolases,
leading to the accumulation of undegraded substrates
within the organelle, which disrupts cellular function.
• Incorrect A: The proteasome degrades ubiquitin-tagged
proteins, not complex lipids within lysosomes.
• Incorrect B: Mitochondrial defects impair energy
production but do not cause substrate accumulation in
lysosomes.
