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
1. Chapter Reference – Chapter 1: The Cell as a Unit of
Health and Disease — The Genome
Stem: A 28-year-old woman’s tumor sequencing shows a
frameshift mutation in a tumor suppressor gene that
truncates the protein and abolishes its nuclear localization
signal. Which consequence best explains how this mutation
promotes tumorigenesis?
A. Increased oncogene transcription due to enhanced
promoter binding
B. Loss of cell-cycle checkpoint control from a
nonfunctional tumor suppressor
C. Gain of a dominant negative effect increasing protein
degradation
D. Activation of telomerase leading to immortalization
Answer: B
,Rationale — correct: Loss of a functional tumor suppressor that
cannot localize to the nucleus prevents it from enforcing cell-
cycle checkpoints (e.g., p53/Rb pathways), permitting
unchecked proliferation and genomic instability, promoting
tumorigenesis.
Rationale — A: Enhanced promoter binding is a gain-of-
function oncogene mechanism, not typical of truncating
frameshift mutations in tumor suppressors.
Rationale — C: A dominant negative effect is possible for some
missense mutants but a truncation removing localization signal
more commonly causes loss of function rather than classic
dominant negativity.
Rationale — D: Telomerase activation can contribute to
immortalization but is not the direct expected consequence of
losing nuclear localization of a tumor suppressor.
Teaching Point: Loss of tumor suppressor nuclear function
disables cell-cycle checkpoints and fosters malignancy.
2. Chapter Reference – Chapter 1 — The Genome
Stem: A patient has a heritable disorder caused by
expansion of a trinucleotide repeat in the 5′ UTR of a gene,
producing reduced protein expression through
hypermethylation. Which mechanism best explains this
epigenetic silencing?
A. Increased histone acetylation across the locus
B. Recruitment of DNA methyltransferases leading to CpG
methylation
C. Loss of promoter CpG islands causing promoter
, displacement
D. Frameshift mutation in coding exon causing nonsense-
mediated decay
Answer: B
Rationale — correct: Expanded repeats (e.g., fragile X type
mechanisms) can recruit DNA methyltransferases, increasing
CpG methylation and chromatin condensation, silencing
transcription and reducing protein expression.
Rationale — A: Histone acetylation is associated with open
chromatin and increased transcription, not silencing.
Rationale — C: CpG island loss is not a recognized mechanism;
rather methylation of CpG islands causes promoter silencing.
Rationale — D: A frameshift causing nonsense-mediated decay
is a post-transcriptional mechanism not linked to repeat-
expansion driven hypermethylation.
Teaching Point: Repeat expansions may silence genes via CpG
methylation and heterochromatin formation.
3. Chapter Reference – Chapter 1 — The Genome
Stem: In cultured fibroblasts exposed to ultraviolet (UV)
light, thymine dimers accumulate. Which DNA repair
pathway is primarily responsible for removing these lesions
in human cells?
A. Base excision repair (BER)
B. Nucleotide excision repair (NER)
C. Mismatch repair (MMR)
D. Nonhomologous end joining (NHEJ)
Answer: B
, Rationale — correct: UV-induced thymine dimers distort the
DNA helix and are specifically recognized and removed by
nucleotide excision repair, which excises an oligonucleotide
segment around the lesion and fills the gap.
Rationale — A: BER repairs small, non-helix-distorting base
lesions (e.g., oxidative damage), not bulky thymine dimers.
Rationale — C: MMR corrects replication mismatches and
insertion/deletion loops, not bulky photoproducts.
Rationale — D: NHEJ repairs double-strand breaks, unrelated to
thymine dimers.
Teaching Point: NER removes bulky helix-distorting lesions like
UV thymine dimers.
4. Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A genetic defect reduces ubiquitin-conjugating
enzyme activity in hepatocytes. Which intracellular process
will be most directly impaired?
A. Lysosomal degradation of extracellular matrix proteins
B. Proteasomal degradation of misfolded cytosolic proteins
C. Endocytosis of receptor-bound hormones
D. Autophagic digestion of organelles via phagolysosomes
Answer: B
Rationale — correct: The ubiquitin–proteasome system tags
misfolded or short-lived cytosolic and nuclear proteins with
ubiquitin for recognition and degradation by the 26S
proteasome; impaired ubiquitination disrupts this pathway
leading to protein accumulation.
Rationale — A: ECM turnover involves extracellular proteases
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1. Chapter Reference – Chapter 1: The Cell as a Unit of
Health and Disease — The Genome
Stem: A 28-year-old woman’s tumor sequencing shows a
frameshift mutation in a tumor suppressor gene that
truncates the protein and abolishes its nuclear localization
signal. Which consequence best explains how this mutation
promotes tumorigenesis?
A. Increased oncogene transcription due to enhanced
promoter binding
B. Loss of cell-cycle checkpoint control from a
nonfunctional tumor suppressor
C. Gain of a dominant negative effect increasing protein
degradation
D. Activation of telomerase leading to immortalization
Answer: B
,Rationale — correct: Loss of a functional tumor suppressor that
cannot localize to the nucleus prevents it from enforcing cell-
cycle checkpoints (e.g., p53/Rb pathways), permitting
unchecked proliferation and genomic instability, promoting
tumorigenesis.
Rationale — A: Enhanced promoter binding is a gain-of-
function oncogene mechanism, not typical of truncating
frameshift mutations in tumor suppressors.
Rationale — C: A dominant negative effect is possible for some
missense mutants but a truncation removing localization signal
more commonly causes loss of function rather than classic
dominant negativity.
Rationale — D: Telomerase activation can contribute to
immortalization but is not the direct expected consequence of
losing nuclear localization of a tumor suppressor.
Teaching Point: Loss of tumor suppressor nuclear function
disables cell-cycle checkpoints and fosters malignancy.
2. Chapter Reference – Chapter 1 — The Genome
Stem: A patient has a heritable disorder caused by
expansion of a trinucleotide repeat in the 5′ UTR of a gene,
producing reduced protein expression through
hypermethylation. Which mechanism best explains this
epigenetic silencing?
A. Increased histone acetylation across the locus
B. Recruitment of DNA methyltransferases leading to CpG
methylation
C. Loss of promoter CpG islands causing promoter
, displacement
D. Frameshift mutation in coding exon causing nonsense-
mediated decay
Answer: B
Rationale — correct: Expanded repeats (e.g., fragile X type
mechanisms) can recruit DNA methyltransferases, increasing
CpG methylation and chromatin condensation, silencing
transcription and reducing protein expression.
Rationale — A: Histone acetylation is associated with open
chromatin and increased transcription, not silencing.
Rationale — C: CpG island loss is not a recognized mechanism;
rather methylation of CpG islands causes promoter silencing.
Rationale — D: A frameshift causing nonsense-mediated decay
is a post-transcriptional mechanism not linked to repeat-
expansion driven hypermethylation.
Teaching Point: Repeat expansions may silence genes via CpG
methylation and heterochromatin formation.
3. Chapter Reference – Chapter 1 — The Genome
Stem: In cultured fibroblasts exposed to ultraviolet (UV)
light, thymine dimers accumulate. Which DNA repair
pathway is primarily responsible for removing these lesions
in human cells?
A. Base excision repair (BER)
B. Nucleotide excision repair (NER)
C. Mismatch repair (MMR)
D. Nonhomologous end joining (NHEJ)
Answer: B
, Rationale — correct: UV-induced thymine dimers distort the
DNA helix and are specifically recognized and removed by
nucleotide excision repair, which excises an oligonucleotide
segment around the lesion and fills the gap.
Rationale — A: BER repairs small, non-helix-distorting base
lesions (e.g., oxidative damage), not bulky thymine dimers.
Rationale — C: MMR corrects replication mismatches and
insertion/deletion loops, not bulky photoproducts.
Rationale — D: NHEJ repairs double-strand breaks, unrelated to
thymine dimers.
Teaching Point: NER removes bulky helix-distorting lesions like
UV thymine dimers.
4. Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A genetic defect reduces ubiquitin-conjugating
enzyme activity in hepatocytes. Which intracellular process
will be most directly impaired?
A. Lysosomal degradation of extracellular matrix proteins
B. Proteasomal degradation of misfolded cytosolic proteins
C. Endocytosis of receptor-bound hormones
D. Autophagic digestion of organelles via phagolysosomes
Answer: B
Rationale — correct: The ubiquitin–proteasome system tags
misfolded or short-lived cytosolic and nuclear proteins with
ubiquitin for recognition and degradation by the 26S
proteasome; impaired ubiquitination disrupts this pathway
leading to protein accumulation.
Rationale — A: ECM turnover involves extracellular proteases
