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 child presents with extreme sun sensitivity and
multiple early skin cancers. Genetic testing reveals defective
removal of UV-induced pyrimidine dimers. Which DNA repair
pathway is most likely defective?
A. Base-excision repair
B. Nucleotide-excision repair
C. Mismatch repair
D. Homologous recombination repair
Correct Answer: B
Rationale (correct): Nucleotide-excision repair (NER) recognizes
and removes bulky helix-distorting lesions such as UV-induced
pyrimidine dimers; defects in NER underlie xeroderma
pigmentosum and marked UV sensitivity. Robbins describes
,NER as the principal system for excising large DNA adducts.
A (wrong): Base-excision repair corrects small, non-helix-
distorting base lesions (e.g., oxidative damage), not bulky UV
dimers.
C (wrong): Mismatch repair fixes replication errors (base–base
mismatches and small insertion/deletion loops), not large UV
lesions.
D (wrong): Homologous recombination repairs double-strand
breaks using a sister chromatid template; it does not remove
UV pyrimidine dimers.
Teaching Point: NER removes bulky DNA lesions (e.g.,
pyrimidine dimers); its failure causes xeroderma pigmentosum.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
(DNA Repair Mechanisms / Xeroderma Pigmentosum).
2. Chapter 1 — The Genome
Stem: A colorectal tumor shows high microsatellite instability.
Methylation analysis reveals hypermethylation of a DNA
mismatch repair gene promoter. Which epigenetic mechanism
best explains the gene silencing?
A. CpG island DNA methylation in the promoter
B. Histone acetylation at the promoter
C. A point mutation in the coding region of the gene
D. Increased microRNA targeting of the mRNA
Correct Answer: A
,Rationale (correct): DNA methylation of CpG islands in gene
promoters represses transcription and can silence tumor-
suppressor or repair genes; promoter hypermethylation of
MMR genes causes deficient repair and microsatellite
instability. Robbins emphasizes DNA methylation as a common
epigenetic silencing mechanism in cancers.
B (wrong): Histone acetylation is associated with transcriptional
activation, not silencing; deacetylation is repressive.
C (wrong): A point mutation alters coding sequence but
epigenetic methylation explains reversible transcriptional
silencing.
D (wrong): microRNAs regulate mRNA stability/translation but
promoter CpG methylation is the canonical mechanism for
gene silencing seen here.
Teaching Point: Promoter CpG methylation silences genes and
contributes to cancer-related loss of function.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
(Epigenetic Alterations).
3. Chapter 1 — The Genome
Stem: A malignant tumor assay shows high telomerase (TERT)
activity compared with surrounding normal tissue. How does
telomerase activity promote cancer cell survival?
A. It enhances DNA mismatch repair fidelity.
B. It prevents telomere shortening, enabling continued
replication.
, C. It directly blocks pro-apoptotic BCL-2 family proteins.
D. It increases homologous recombination frequency.
Correct Answer: B
Rationale (correct): Telomerase adds telomeric repeats to
chromosome ends, preventing progressive telomere shortening
that would otherwise limit replicative capacity; reactivation of
telomerase is a common mechanism for cellular immortality in
cancers. Robbins describes telomerase upregulation as
permitting unlimited replication.
A (wrong): Telomerase does not directly influence mismatch
repair fidelity.
C (wrong): Telomerase does not directly inhibit BCL-2 family
proteins; apoptosis regulation is separate.
D (wrong): Telomerase does not primarily increase homologous
recombination frequency.
Teaching Point: Telomerase maintains telomeres, supporting
unlimited cancer cell replication.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
(Telomeres and Telomerase).
4. Chapter 1 — Cellular Housekeeping
Stem: A neurodegenerative disease shows accumulation of
large protein aggregates and damaged organelles in neurons
despite intact proteasome markers. Which degradative
pathway is most likely impaired?
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 child presents with extreme sun sensitivity and
multiple early skin cancers. Genetic testing reveals defective
removal of UV-induced pyrimidine dimers. Which DNA repair
pathway is most likely defective?
A. Base-excision repair
B. Nucleotide-excision repair
C. Mismatch repair
D. Homologous recombination repair
Correct Answer: B
Rationale (correct): Nucleotide-excision repair (NER) recognizes
and removes bulky helix-distorting lesions such as UV-induced
pyrimidine dimers; defects in NER underlie xeroderma
pigmentosum and marked UV sensitivity. Robbins describes
,NER as the principal system for excising large DNA adducts.
A (wrong): Base-excision repair corrects small, non-helix-
distorting base lesions (e.g., oxidative damage), not bulky UV
dimers.
C (wrong): Mismatch repair fixes replication errors (base–base
mismatches and small insertion/deletion loops), not large UV
lesions.
D (wrong): Homologous recombination repairs double-strand
breaks using a sister chromatid template; it does not remove
UV pyrimidine dimers.
Teaching Point: NER removes bulky DNA lesions (e.g.,
pyrimidine dimers); its failure causes xeroderma pigmentosum.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
(DNA Repair Mechanisms / Xeroderma Pigmentosum).
2. Chapter 1 — The Genome
Stem: A colorectal tumor shows high microsatellite instability.
Methylation analysis reveals hypermethylation of a DNA
mismatch repair gene promoter. Which epigenetic mechanism
best explains the gene silencing?
A. CpG island DNA methylation in the promoter
B. Histone acetylation at the promoter
C. A point mutation in the coding region of the gene
D. Increased microRNA targeting of the mRNA
Correct Answer: A
,Rationale (correct): DNA methylation of CpG islands in gene
promoters represses transcription and can silence tumor-
suppressor or repair genes; promoter hypermethylation of
MMR genes causes deficient repair and microsatellite
instability. Robbins emphasizes DNA methylation as a common
epigenetic silencing mechanism in cancers.
B (wrong): Histone acetylation is associated with transcriptional
activation, not silencing; deacetylation is repressive.
C (wrong): A point mutation alters coding sequence but
epigenetic methylation explains reversible transcriptional
silencing.
D (wrong): microRNAs regulate mRNA stability/translation but
promoter CpG methylation is the canonical mechanism for
gene silencing seen here.
Teaching Point: Promoter CpG methylation silences genes and
contributes to cancer-related loss of function.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
(Epigenetic Alterations).
3. Chapter 1 — The Genome
Stem: A malignant tumor assay shows high telomerase (TERT)
activity compared with surrounding normal tissue. How does
telomerase activity promote cancer cell survival?
A. It enhances DNA mismatch repair fidelity.
B. It prevents telomere shortening, enabling continued
replication.
, C. It directly blocks pro-apoptotic BCL-2 family proteins.
D. It increases homologous recombination frequency.
Correct Answer: B
Rationale (correct): Telomerase adds telomeric repeats to
chromosome ends, preventing progressive telomere shortening
that would otherwise limit replicative capacity; reactivation of
telomerase is a common mechanism for cellular immortality in
cancers. Robbins describes telomerase upregulation as
permitting unlimited replication.
A (wrong): Telomerase does not directly influence mismatch
repair fidelity.
C (wrong): Telomerase does not directly inhibit BCL-2 family
proteins; apoptosis regulation is separate.
D (wrong): Telomerase does not primarily increase homologous
recombination frequency.
Teaching Point: Telomerase maintains telomeres, supporting
unlimited cancer cell replication.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
(Telomeres and Telomerase).
4. Chapter 1 — Cellular Housekeeping
Stem: A neurodegenerative disease shows accumulation of
large protein aggregates and damaged organelles in neurons
despite intact proteasome markers. Which degradative
pathway is most likely impaired?
