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 28-year-old woman undergoes whole-exome
sequencing after recurrent early-onset breast cancer in the
family. The report shows a single-nucleotide polymorphism
(SNP) in a noncoding region that is associated with altered gene
expression. Which mechanism most plausibly explains how a
noncoding SNP changes gene expression?
A. Altered amino acid sequence of a transcription factor
B. Change in promoter or enhancer binding affecting
transcriptional regulation
C. Increased rate of mRNA translation due to codon usage bias
D. Frame-shift mutation producing truncated protein
Correct Answer: B
,Rationale (correct): Noncoding variants frequently affect
regulatory DNA (promoters/enhancers) or transcription factor
binding sites, altering gene transcription without changing
protein sequence, a mechanism emphasized in Robbins (Ch.1).
Rationale (A): Altered amino acid sequence implies a coding-
region variant; noncoding SNPs do not change amino acid
sequence.
Rationale (C): Codon usage affects translation only when
coding sequence is changed; noncoding SNPs do not change
codons.
Rationale (D): Frame-shift requires insertion/deletion in coding
sequence; a noncoding SNP cannot cause frame-shift.
Teaching Point: Noncoding variants often act by modulating
regulatory element activity.
Citation: Robbins & Cotran, 10th Ed., Ch.1 — The Genome.
Google Books
2. Chapter 1 — The Genome
Stem: A tumor biopsy is found to have copy number
amplification of the MYC locus. Which immediate cellular
consequence best explains how gene amplification promotes
tumor progression?
A. Increased stability of microRNA regulators of MYC
B. Overexpression of MYC protein leading to dysregulated cell
proliferation
C. Genome-wide hypomethylation that prevents transcription
,factor binding
D. Increased rate of alternative splicing producing novel tumor
suppressors
Correct Answer: B
Rationale (correct): Gene amplification increases gene dosage
and commonly drives overexpression of oncoproteins (e.g.,
MYC), promoting proliferation and neoplastic progression
(Robbins Ch.1 discussion of genetic variation and cancer).
Rationale (A): Amplification increases gene copies; it does not
specifically stabilize microRNAs.
Rationale (C): Copy number changes do not directly cause
hypomethylation genome-wide; epigenetic changes are
separate mechanisms.
Rationale (D): Alternative splicing alterations are not a direct
consequence of locus amplification.
Teaching Point: Gene amplification raises oncogene dosage and
protein expression.
Citation: Robbins & Cotran, 10th Ed., Ch.1 — The Genome.
Google Books
3. Chapter 1 — The Genome
Stem: A pediatric patient has a mitochondrial DNA (mtDNA)
mutation causing defective oxidative phosphorylation. Which
feature is most consistent with a pathogenic mtDNA mutation?
A. Inheritance in a strictly Mendelian dominant pattern
, B. Homoplasmy in all maternal relatives with identical disease
severity
C. Heteroplasmy with variable clinical expression among tissues
D. Exclusive paternal transmission of the defect
Correct Answer: C
Rationale (correct): mtDNA mutations show heteroplasmy
(mixture of normal and mutant mtDNA) and variable
penetrance across tissues, affecting tissues with high energy
demand — a central Robbins point on mitochondrial genetics.
Rationale (A): mtDNA inheritance is non-Mendelian and
maternally transmitted, not typical nuclear dominant
inheritance.
Rationale (B): Homoplasmy with identical severity is
uncommon; heteroplasmy explains variable clinical expression.
Rationale (D): Paternal transmission of mtDNA is extremely
rare; mtDNA is typically maternally inherited.
Teaching Point: Heteroplasmy explains variable expression of
mitochondrial disorders.
Citation: Robbins & Cotran, 10th Ed., Ch.1 — The Genome
(mitochondrial genetics). Google Books
4. Chapter 1 — Cellular Housekeeping
Stem: A cell exposed to mild hypoxia reduces its energy
consumption by downregulating protein synthesis. Which
cellular structure is primarily responsible for reducing global
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 28-year-old woman undergoes whole-exome
sequencing after recurrent early-onset breast cancer in the
family. The report shows a single-nucleotide polymorphism
(SNP) in a noncoding region that is associated with altered gene
expression. Which mechanism most plausibly explains how a
noncoding SNP changes gene expression?
A. Altered amino acid sequence of a transcription factor
B. Change in promoter or enhancer binding affecting
transcriptional regulation
C. Increased rate of mRNA translation due to codon usage bias
D. Frame-shift mutation producing truncated protein
Correct Answer: B
,Rationale (correct): Noncoding variants frequently affect
regulatory DNA (promoters/enhancers) or transcription factor
binding sites, altering gene transcription without changing
protein sequence, a mechanism emphasized in Robbins (Ch.1).
Rationale (A): Altered amino acid sequence implies a coding-
region variant; noncoding SNPs do not change amino acid
sequence.
Rationale (C): Codon usage affects translation only when
coding sequence is changed; noncoding SNPs do not change
codons.
Rationale (D): Frame-shift requires insertion/deletion in coding
sequence; a noncoding SNP cannot cause frame-shift.
Teaching Point: Noncoding variants often act by modulating
regulatory element activity.
Citation: Robbins & Cotran, 10th Ed., Ch.1 — The Genome.
Google Books
2. Chapter 1 — The Genome
Stem: A tumor biopsy is found to have copy number
amplification of the MYC locus. Which immediate cellular
consequence best explains how gene amplification promotes
tumor progression?
A. Increased stability of microRNA regulators of MYC
B. Overexpression of MYC protein leading to dysregulated cell
proliferation
C. Genome-wide hypomethylation that prevents transcription
,factor binding
D. Increased rate of alternative splicing producing novel tumor
suppressors
Correct Answer: B
Rationale (correct): Gene amplification increases gene dosage
and commonly drives overexpression of oncoproteins (e.g.,
MYC), promoting proliferation and neoplastic progression
(Robbins Ch.1 discussion of genetic variation and cancer).
Rationale (A): Amplification increases gene copies; it does not
specifically stabilize microRNAs.
Rationale (C): Copy number changes do not directly cause
hypomethylation genome-wide; epigenetic changes are
separate mechanisms.
Rationale (D): Alternative splicing alterations are not a direct
consequence of locus amplification.
Teaching Point: Gene amplification raises oncogene dosage and
protein expression.
Citation: Robbins & Cotran, 10th Ed., Ch.1 — The Genome.
Google Books
3. Chapter 1 — The Genome
Stem: A pediatric patient has a mitochondrial DNA (mtDNA)
mutation causing defective oxidative phosphorylation. Which
feature is most consistent with a pathogenic mtDNA mutation?
A. Inheritance in a strictly Mendelian dominant pattern
, B. Homoplasmy in all maternal relatives with identical disease
severity
C. Heteroplasmy with variable clinical expression among tissues
D. Exclusive paternal transmission of the defect
Correct Answer: C
Rationale (correct): mtDNA mutations show heteroplasmy
(mixture of normal and mutant mtDNA) and variable
penetrance across tissues, affecting tissues with high energy
demand — a central Robbins point on mitochondrial genetics.
Rationale (A): mtDNA inheritance is non-Mendelian and
maternally transmitted, not typical nuclear dominant
inheritance.
Rationale (B): Homoplasmy with identical severity is
uncommon; heteroplasmy explains variable clinical expression.
Rationale (D): Paternal transmission of mtDNA is extremely
rare; mtDNA is typically maternally inherited.
Teaching Point: Heteroplasmy explains variable expression of
mitochondrial disorders.
Citation: Robbins & Cotran, 10th Ed., Ch.1 — The Genome
(mitochondrial genetics). Google Books
4. Chapter 1 — Cellular Housekeeping
Stem: A cell exposed to mild hypoxia reduces its energy
consumption by downregulating protein synthesis. Which
cellular structure is primarily responsible for reducing global
