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
1. Question: A 46-year-old man’s tumor harbors a point
mutation that constitutively activates a receptor tyrosine
kinase; the oncogenic change is most consistent with
which genomic alteration mechanism?
A. Loss-of-function mutation in a tumor suppressor gene
B. Gain-of-function point mutation in a proto-oncogene
C. Large chromosomal deletion removing a growth-
inhibitory locus
D. Promoter hypermethylation causing gene silencing
Correct Answer: B
Rationale — Correct: A single point mutation that makes a
receptor constitutively active is classically a gain-of-function
mutation transforming a proto-oncogene to an oncogene;
,Robbins describes such activating point mutations in oncogenes
(e.g., RAS, RET).
Rationale — A: Loss-of-function tumor suppressor changes
typically require two hits and result in reduced inhibition, not
constitutive receptor activation.
Rationale — C: Large deletions usually inactivate suppressors
or remove genes; they do not produce a constitutively active
receptor.
Rationale — D: Promoter hypermethylation silences genes
(loss-of-function), not create constitutive activation.
Teaching Point: Oncogenes arise by gain-of-function mutations
that cause constitutive signaling.
Citation: Robbins Ch.1, Section “The Genome” (oncogenes vs
tumor suppressors; activating mutations).
2. Chapter 1 — The Genome
Question: A patient has a defect in nucleotide excision
repair and develops multiple skin cancers after UV
exposure. Which type of DNA lesion is least effectively
repaired by this pathway?
A. Thymine dimers caused by UV radiation
B. Single-base mismatches from replication errors
C. Bulky adducts caused by chemical carcinogens
D. Pyrimidine–pyrimidone photoproducts
Correct Answer: B
,Rationale — Correct: Nucleotide excision repair (NER) removes
bulky helix-distorting lesions such as thymine dimers and bulky
adducts; single-base mismatches are handled by the mismatch
repair pathway, not NER.
Rationale — A: Thymine dimers are classic NER substrates.
Rationale — C: Bulky chemical adducts are removed by NER.
Rationale — D: Photoproducts of pyrimidines are corrected by
NER.
Teaching Point: NER removes bulky, helix-distorting lesions;
mismatch repair fixes replication mismatches.
Citation: Robbins Ch.1, Section “The Genome” (DNA repair
pathways).
3. Chapter 1 — Cellular Housekeeping
Question: A neuron accumulates lipofuscin in lysosomes
with age. Which cellular process best explains this
accumulation?
A. Increased autophagy of damaged organelles with
defective lysosomal degradation
B. Enhanced proteasomal activity digesting aggregated
proteins
C. Increased mitochondrial biogenesis clearing oxidized
lipids
D. Upregulated exocytosis of waste material
Correct Answer: A
, Rationale — Correct: Lipofuscin accumulates in lysosomes
when autophagy delivers damaged organelles and lysosomal
degradation is incomplete—commonly in long-lived cells like
neurons. Robbins describes lipofuscin as wear-and-tear
pigment from incomplete lysosomal digestion.
Rationale — B: Proteasomes degrade soluble proteins, not
form lipofuscin within lysosomes.
Rationale — C: Mitochondrial biogenesis does not clear
oxidized lipid residues accumulating as lipofuscin.
Rationale — D: Exocytosis is not the main route for removing
lipofuscin from long-lived cells.
Teaching Point: Lipofuscin results from incomplete lysosomal
degradation of cellular debris.
Citation: Robbins Ch.1, Section “Cellular Housekeeping”
(lysosomes, lipofuscin).
4. Chapter 1 — Cellular Housekeeping
Question: A patient’s muscle biopsy shows accumulation
of ubiquitin-positive inclusions. Which intracellular quality-
control system is most likely impaired?
A. Lysosomal autophagy pathway
B. Ubiquitin–proteasome system
C. Endoplasmic reticulum-associated degradation (ERAD)
with intact proteasome
D. Mitochondrial unfolded protein response
Correct Answer: B
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
1. Question: A 46-year-old man’s tumor harbors a point
mutation that constitutively activates a receptor tyrosine
kinase; the oncogenic change is most consistent with
which genomic alteration mechanism?
A. Loss-of-function mutation in a tumor suppressor gene
B. Gain-of-function point mutation in a proto-oncogene
C. Large chromosomal deletion removing a growth-
inhibitory locus
D. Promoter hypermethylation causing gene silencing
Correct Answer: B
Rationale — Correct: A single point mutation that makes a
receptor constitutively active is classically a gain-of-function
mutation transforming a proto-oncogene to an oncogene;
,Robbins describes such activating point mutations in oncogenes
(e.g., RAS, RET).
Rationale — A: Loss-of-function tumor suppressor changes
typically require two hits and result in reduced inhibition, not
constitutive receptor activation.
Rationale — C: Large deletions usually inactivate suppressors
or remove genes; they do not produce a constitutively active
receptor.
Rationale — D: Promoter hypermethylation silences genes
(loss-of-function), not create constitutive activation.
Teaching Point: Oncogenes arise by gain-of-function mutations
that cause constitutive signaling.
Citation: Robbins Ch.1, Section “The Genome” (oncogenes vs
tumor suppressors; activating mutations).
2. Chapter 1 — The Genome
Question: A patient has a defect in nucleotide excision
repair and develops multiple skin cancers after UV
exposure. Which type of DNA lesion is least effectively
repaired by this pathway?
A. Thymine dimers caused by UV radiation
B. Single-base mismatches from replication errors
C. Bulky adducts caused by chemical carcinogens
D. Pyrimidine–pyrimidone photoproducts
Correct Answer: B
,Rationale — Correct: Nucleotide excision repair (NER) removes
bulky helix-distorting lesions such as thymine dimers and bulky
adducts; single-base mismatches are handled by the mismatch
repair pathway, not NER.
Rationale — A: Thymine dimers are classic NER substrates.
Rationale — C: Bulky chemical adducts are removed by NER.
Rationale — D: Photoproducts of pyrimidines are corrected by
NER.
Teaching Point: NER removes bulky, helix-distorting lesions;
mismatch repair fixes replication mismatches.
Citation: Robbins Ch.1, Section “The Genome” (DNA repair
pathways).
3. Chapter 1 — Cellular Housekeeping
Question: A neuron accumulates lipofuscin in lysosomes
with age. Which cellular process best explains this
accumulation?
A. Increased autophagy of damaged organelles with
defective lysosomal degradation
B. Enhanced proteasomal activity digesting aggregated
proteins
C. Increased mitochondrial biogenesis clearing oxidized
lipids
D. Upregulated exocytosis of waste material
Correct Answer: A
, Rationale — Correct: Lipofuscin accumulates in lysosomes
when autophagy delivers damaged organelles and lysosomal
degradation is incomplete—commonly in long-lived cells like
neurons. Robbins describes lipofuscin as wear-and-tear
pigment from incomplete lysosomal digestion.
Rationale — B: Proteasomes degrade soluble proteins, not
form lipofuscin within lysosomes.
Rationale — C: Mitochondrial biogenesis does not clear
oxidized lipid residues accumulating as lipofuscin.
Rationale — D: Exocytosis is not the main route for removing
lipofuscin from long-lived cells.
Teaching Point: Lipofuscin results from incomplete lysosomal
degradation of cellular debris.
Citation: Robbins Ch.1, Section “Cellular Housekeeping”
(lysosomes, lipofuscin).
4. Chapter 1 — Cellular Housekeeping
Question: A patient’s muscle biopsy shows accumulation
of ubiquitin-positive inclusions. Which intracellular quality-
control system is most likely impaired?
A. Lysosomal autophagy pathway
B. Ubiquitin–proteasome system
C. Endoplasmic reticulum-associated degradation (ERAD)
with intact proteasome
D. Mitochondrial unfolded protein response
Correct Answer: B
